Viruses

11 pages, 623 KiB

Open AccessArticle

Comparative Analysis of the Clinical Presentation of Individuals Who Test Positive or Negative for SARS-CoV-2: Results from a Test Street Study

by Pantea Kiani, Pauline A. Hendriksen, Andy J. Kim, Johan Garssen and Joris C. Verster

Viruses 2024, 16(7), 1031; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071031 (registering DOI) - 26 Jun 2024

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Abstract

The common cold, the flu, and the 2019 coronavirus disease (COVID-19) have many symptoms in common. As such, without testing for severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2), it is difficult to conclude whether or not one is infected with SARS-CoV-2. The aim of the current [...] Read more.

The common cold, the flu, and the 2019 coronavirus disease (COVID-19) have many symptoms in common. As such, without testing for severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2), it is difficult to conclude whether or not one is infected with SARS-CoV-2. The aim of the current study was to compare the presence and severity of COVID-19-related symptoms among those who tested positive or negative for the beta variant of SARS-CoV-2 (B.1.351) and identify the clinical presentation with the greatest likelihood of testing positive for SARS-CoV-2. n = 925 individuals that were tested for SARS-CoV-2 at Dutch mass testing sites (i.e., test streets) were invited to complete a short online survey. The presence and severity of 17 COVID-19-related symptoms were assessed. In addition, mood, health correlates, and quality of life were assessed for the week before the test. Of the sample, n = 88 tested positive and n = 837 tested negative for SARS-CoV-2. Individuals who tested positive for SARS-CoV-2 reported experiencing a significantly greater number, as well as greater overall symptom severity, compared to individuals who tested negative for SARS-CoV-2. A binary logistic regression analysis revealed that increased severity levels of congestion, coughing, shivering, or loss of smell were associated with an increase in the odds of testing positive for SARS-CoV-2, whereas an increase in the severity levels of runny nose, sore throat, or fatigue were associated with an increase in the odds of testing negative for SARS-CoV-2. No significant differences in mood or health correlates were found between those who tested positive or negative for SARS-CoV-2, except for a significantly higher stress score among those who tested negative for SARS-CoV-2. In conclusion, individuals that tested positive for SARS-CoV-2 experienced a significantly greater number and more severe COVID-19-related symptoms compared to those who tested negative for SARS-CoV-2. Experiencing shivering and loss of smell may be the best indicators for increased likelihood of testing positive for SARS-CoV-2. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

17 pages, 3880 KiB

Open AccessArticle

Designing a Conserved Immunogenic Peptide Construct from the Nucleocapsid Protein of Puumala orthohantavirus

by Ayushi Sehgal, Diksha Sharma, Neha Kaushal, Yogita Gupta, Ekaterina Martynova, Emmanuel Kabwe, Sara Chandy, Albert Rizvanov, Svetlana Khaiboullina and Manoj Baranwal

Viruses 2024, 16(7), 1030; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071030 (registering DOI) - 26 Jun 2024

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Abstract

Puumala orthohantavirus (PUUV) is an emerging zoonotic virus endemic to Europe and Russia that causes nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome (HFRS). There are limited options for treatment and diagnosis of orthohantavirus infection, making the search for potential [...] Read more.

Puumala orthohantavirus (PUUV) is an emerging zoonotic virus endemic to Europe and Russia that causes nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome (HFRS). There are limited options for treatment and diagnosis of orthohantavirus infection, making the search for potential immunogenic candidates crucial. In the present work, various bioinformatics tools were employed to design conserved immunogenic peptides containing multiple epitopes of PUUV nucleocapsid protein. Eleven conserved peptides (90% conservancy) of the PUUV nucleocapsid protein were identified. Three conserved peptides containing multiple T and B cell epitopes were selected using a consensus epitope prediction algorithm. Molecular docking using the HPEP dock server demonstrated strong binding interactions between the epitopes and HLA molecules (ten alleles for each class I and II HLA). Moreover, an analysis of population coverage using the IEDB database revealed that the identified peptides have over 90% average population coverage across six continents. Molecular docking and simulation analysis reveal a stable interaction with peptide constructs of chosen immunogenic peptides and Toll-like receptor-4. These computational analyses demonstrate selected peptides’ immunogenic potential, which needs to be validated in different experimental systems. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Vaccines against Viruses: From Network Medicine to Clinical Experimentation 2nd Edition)

22 pages, 5934 KiB

Open AccessArticle

A T-Cell-Derived 3-Gene Signature Distinguishes SARS-CoV-2 from Common Respiratory Viruses

by Yang Li, Xinya Tao, Sheng Ye, Qianchen Tai, Yu-Ang You, Xinting Huang, Mifang Liang, Kai Wang, Haiyan Wen, Chong You, Yan Zhang and Xiaohua Zhou

Viruses 2024, 16(7), 1029; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071029 (registering DOI) - 26 Jun 2024

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Abstract

Research on the host responses to respiratory viruses could help develop effective interventions and therapies against the current and future pandemics from the host perspective. To explore the pathogenesis that distinguishes SARS-CoV-2 infections from other respiratory viruses, we performed a multi-cohort analysis with [...] Read more.

Research on the host responses to respiratory viruses could help develop effective interventions and therapies against the current and future pandemics from the host perspective. To explore the pathogenesis that distinguishes SARS-CoV-2 infections from other respiratory viruses, we performed a multi-cohort analysis with integrated bioinformatics and machine learning. We collected 3730 blood samples from both asymptomatic and symptomatic individuals infected with SARS-CoV-2, seasonal human coronavirus (sHCoVs), influenza virus (IFV), respiratory syncytial virus (RSV), or human rhinovirus (HRV) across 15 cohorts. First, we identified an enhanced cellular immune response but limited interferon activities in SARS-CoV-2 infection, especially in asymptomatic cases. Second, we identified a SARS-CoV-2-specific 3-gene signature (CLSPN, RBBP6, CCDC91) that was predominantly expressed by T cells, could distinguish SARS-CoV-2 infection, including Omicron, from other common respiratory viruses regardless of symptoms, and was predictive of SARS-CoV-2 infection before detectable viral RNA on RT-PCR testing in a longitude follow-up study. Thereafter, a user-friendly online tool, based on datasets collected here, was developed for querying a gene of interest across multiple viral infections. Our results not only identify a unique host response to the viral pathogenesis in SARS-CoV-2 but also provide insights into developing effective tools against viral pandemics from the host perspective. Full article

(This article belongs to the Special Issue Advanced Strategies against SARS-CoV-2 Variants and Future Emerging Virus Outbreaks)

14 pages, 1468 KiB

Open AccessArticle

Long COVID Clusters of Symptoms Persist beyond Two Years after Infection: Insights from the CARDIO COVID 20–21 Registry

by Juan Pablo Arango-Ibanez, Brayan Daniel Córdoba-Melo, Juliana María Gutiérrez Posso, Mario Miguel Barbosa-Rengifo, Cesar J. Herrera, Miguel Angel Quintana Da Silva, Andrés Felipe Buitrago, María Lorena Coronel Gilio, Freddy Pow-Chong-Long and Juan Esteban Gómez-Mesa

Viruses 2024, 16(7), 1028; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071028 - 26 Jun 2024

Viewed by 114

Abstract

Long COVID presents with diverse symptoms after COVID-19. Different clusters of symptoms have been reported; however, their persistence beyond 2 years after COVID-19 remains unclear. In this cohort study, we prospectively evaluated individuals with previous severe COVID-19 presenting with long COVID at a [...] Read more.

Long COVID presents with diverse symptoms after COVID-19. Different clusters of symptoms have been reported; however, their persistence beyond 2 years after COVID-19 remains unclear. In this cohort study, we prospectively evaluated individuals with previous severe COVID-19 presenting with long COVID at a two-year follow-up. We characterized the included patients and performed a cluster analysis of symptoms through multiple correspondence analysis and hierarchical clustering. A total of 199 patients with long COVID were included. The median age was 58 years (48–69), 56% were male, and the median follow-up time since the COVID-19 diagnosis was 26 months (IQR: 25, 27). Three symptom clusters were identified: Cluster 1 is characterized by fatigue, myalgia/arthralgia, a low prevalence of symptoms, and a lack of specific symptoms; Cluster 2 is defined by a high prevalence of fatigue, myalgia/arthralgia, and cardiorespiratory symptoms, including palpitations, shortness of breath, cough, and chest pain; and Cluster 3 is demonstrated a high prevalence of ageusia, anosmia, fatigue, and cardiorespiratory symptoms. Our study reinforces the concept of symptom clustering in long COVID, providing evidence that these clusters may persist beyond two years after a COVID-19 diagnosis. This highlights the chronic and debilitating nature of long COVID and the importance of developing strategies to mitigate symptoms in these patients. Full article

(This article belongs to the Special Issue COVID-19: Prognosis and Long-Term Sequelae, 2nd Edition)

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25 pages, 4074 KiB

Open AccessArticle

Chandipura Virus Forms Cytoplasmic Inclusion Bodies through Phase Separation and Proviral Association of Cellular Protein Kinase R and Stress Granule Protein TIA-1

by Sharmistha Sarkar, Surajit Ganguly, Nirmal K. Ganguly, Debi P. Sarkar and Nishi Raj Sharma

Viruses 2024, 16(7), 1027; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071027 - 26 Jun 2024

Viewed by 113

Abstract

Negative-strand RNA viruses form cytoplasmic inclusion bodies (IBs) representing virus replication foci through phase separation or biomolecular condensation of viral and cellular proteins, as a hallmark of their infection. Alternatively, mammalian cells form stalled mRNA containing antiviral stress granules (SGs), as a consequence [...] Read more.

Negative-strand RNA viruses form cytoplasmic inclusion bodies (IBs) representing virus replication foci through phase separation or biomolecular condensation of viral and cellular proteins, as a hallmark of their infection. Alternatively, mammalian cells form stalled mRNA containing antiviral stress granules (SGs), as a consequence of phosphorylation of eukaryotic initiation factor 2α (eIF2α) through condensation of several RNA-binding proteins including TIA-1. Whether and how Chandipura virus (CHPV), an emerging human pathogen causing influenza-like illness, coma and death, forms IBs and evades antiviral SGs remain unknown. By confocal imaging on CHPV-infected Vero-E6 cells, we found that CHPV infection does not induce formation of distinct canonical SGs. Instead, CHPV proteins condense and co-localize together with SG proteins to form heterogeneous IBs, which ensued independent of the activation of eIF2α and eIF2α kinase, protein kinase R (PKR). Interestingly, siRNA-mediated depletion of PKR or TIA-1 significantly decreased viral transcription and virion production. Moreover, CHPV infection also caused condensation and recruitment of PKR to IBs. Compared to SGs, IBs exhibited significant rapidity in disassembly dynamics. Altogether, our study demonstrating that CHPV replication co-optimizes with SG proteins and revealing an unprecedented proviral role of TIA-1/PKR may have implications in understanding the mechanisms regulating CHPV-IB formation and designing antiviral therapeutics. Importance: CHPV is an emerging tropical pathogen reported to cause acute influenza-like illness and encephalitis in children with a very high mortality rate of ~70%. Lack of vaccines and an effective therapy against CHPV makes it a potent pathogen for causing an epidemic in tropical parts of globe. Given these forewarnings, it is of paramount importance that CHPV biology must be understood comprehensively. Targeting of host factors offers several advantages over targeting the viral components due to the generally higher mutation rate in the viral genome. In this study, we aimed at understanding the role of SGs forming cellular RNA-binding proteins in CHPV replication. Our study helps understand participation of cellular factors in CHPV replication and could help develop effective therapeutics against the virus. Full article

(This article belongs to the Section General Virology)

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13 pages, 266 KiB

Open AccessReview

The Influence of Simulated Organic Matter on the Inactivation of Viruses: A Review

by Christina Allingham, Miyu Taniguchi, Amanda J. Kinchla and Matthew D. Moore

Viruses 2024, 16(7), 1026; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071026 - 26 Jun 2024

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Abstract

Viruses impose a significant public health burden globally, and one of the key elements in controlling their transmission is the ability to inactivate them using disinfectants. However, numerous challenges to inactivating foodborne viruses exist due to inherent viral characteristics (such as recalcitrance to [...] Read more.

Viruses impose a significant public health burden globally, and one of the key elements in controlling their transmission is the ability to inactivate them using disinfectants. However, numerous challenges to inactivating foodborne viruses exist due to inherent viral characteristics (such as recalcitrance to commonly used inactivation agents) and external factors (such as improper cleaning before application of inactivation agent, improper contact time, etc.). Given the potential for improper application of disinfectants (such as shorter than recommended contact time, improper disinfectant concentration, etc.), understanding the performance of a disinfectant in the presence of an organic load is important. To accomplish this, the introduction of simulated organic loads is often used when studying the efficacy of a disinfectant against different viruses. However, the different types of simulated organic loads used in foodborne virus inactivation studies or their relative effects on inactivation have not been reviewed. The purpose of this review is to survey different simulated organic load formulations used in studying foodborne virus inactivation, as well as present and compare the influence of these different formulations on viral inactivation. The findings included in this review suggest that many simulated organic load formulations can reduce disinfectants’ efficacy against viruses. Based on the findings in this review, blood, particularly serum or feces, are among the most commonly used and efficacious forms of simulated organic load in many tests. Full article

(This article belongs to the Special Issue Human Norovirus 2024)

14 pages, 595 KiB

Open AccessArticle

Severe COVID-19 Outcomes in Five Latin American Countries in the Postvaccination Era

by Guilherme Silva Julian, Júlia Spinardi, Melissa Diaz-Puentes, Diana Buitrago, Ida Caterina García and Moe H. Kyaw

Viruses 2024, 16(7), 1025; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071025 - 26 Jun 2024

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Abstract

We conducted a multicountry retrospective study using data from COVID-19 national surveillance databases to analyze clinical profiles, hospitalization rates, intensive care unit (ICU) admissions, utilization of ventilatory support, and mortality rates in five Latin American countries in the context of COVID-19 vaccination implementation. [...] Read more.

We conducted a multicountry retrospective study using data from COVID-19 national surveillance databases to analyze clinical profiles, hospitalization rates, intensive care unit (ICU) admissions, utilization of ventilatory support, and mortality rates in five Latin American countries in the context of COVID-19 vaccination implementation. We analyzed the sociodemographic characteristics, comorbidities, clinical outcomes, and vaccination status of laboratory-confirmed COVID-19 cases from January 2021 to December 2022. We calculated the yearly and quarterly hospitalization rates per 1000 confirmed COVID-19 cases and ICU admissions, use of mechanical ventilators, and mortality rates per 1000 hospitalized cases, with their corresponding 95% confidence interval (CI) of 38,852,831 confirmed COVID-19 cases. Rates of hospitalization, ICU admission, ventilatory support, and death were higher among males than among females (38.2 vs. 32.4, 148.4 vs. 117.7, 282.9 vs. 236.2, and 346.9 vs. 320.1 per 1000, respectively); higher in 2021 than in 2022 (50.7 vs. 19.9, 207.8 vs. 58.2, 441.5 vs. 114.9, and 352.5 vs. 285.2 per 1000, respectively); and in the >50 age group (range: 5.7–18.6, 20.1–71.5, 12.2–67.9, and 353.1–577.4, per 1000) than the <50 age group (range: 2.2–9.3, 5.4–33.2, 41.4–135.8, and 22–243.5 per 1000). Hypertension and diabetes mellitus were the most common comorbidities in Mexico and Colombia. Prevention and treatment strategies for these case profiles could bring benefits from a public health perspective. Full article

(This article belongs to the Special Issue COVID-19 Complications and Co-infections)

12 pages, 1340 KiB

Open AccessArticle

Bovine Alphaherpesvirus 1, Bovine Alphaherpesvirus 5 and Bubaline Alphaherpesvirus 1 in Palatine Tonsils from Water Buffaloes in Northern Brazil and Possible Links with the Origin of Bovine Alphaherpesvirus Type 5

by Bruna Paredes-Galarza, Martha T. Oliveira, Francine B. Timm, Nicole V. Stone, Lina Violet-Lozano, Richard S. Salvato, Nícolas D. Müller, Bruno A. Prandi, Raíssa Gasparetto, Michelen Gonçalves, María A. S. Teixeira, Márcio A. O. Moura, Gabriela Riet-Correa, Valíria D. Cerqueira, Pedro S. Bezerra, Jr., Fabrício S. Campos, Ana C. Franco and Paulo M. Roehe

Viruses 2024, 16(7), 1024; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071024 - 26 Jun 2024

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Abstract

Herpesviruses are significant pathogens of ruminants. In water buffaloes (Bubalus bubalis), however, herpesviruses have not been thoroughly studied. Although bubaline alphaherpesvirus 1 (BuAHV1) and bovine alphaherpesvirus 1 (BoAHV1) have already been recovered from water buffaloes, to date, no reports on the [...] Read more.

Herpesviruses are significant pathogens of ruminants. In water buffaloes (Bubalus bubalis), however, herpesviruses have not been thoroughly studied. Although bubaline alphaherpesvirus 1 (BuAHV1) and bovine alphaherpesvirus 1 (BoAHV1) have already been recovered from water buffaloes, to date, no reports on the occurrence of bovine alphaherpesvirus 5 (BoAHV5) in these animals have been published. Therefore, the aim of this study was to search for BuAHV1, BoAHV1, and BoAHV5 in palatine tonsils of apparently healthy water buffaloes from the Pará state, Northern Brazil. Tissue samples of tonsils (n = 293) were screened by a nested PCR (nPCR) targeting a region of UL44 (gC coding gene), followed by sequencing, to detect and differentiate between the viral types. Viral genome segments were detected in 18 out of 293 (6.1%) of the palatine tonsil samples. Two animals carried genomes of BoAHV1 only, eleven animals carried BoAHV5 genomes only, and four animals carried BuAHV1 only. Another animal had both BoAHV1 and BoAHV5 genomes in its tonsils. No infectious virus could be recovered from any of the samples. The BuAHV1 sequences identified here were more closely related to BuAHV1 genomes identified in India. Phylogenetic analyses suggested a closer relationship between the recovered BoAHV5 and BuAHV1 genomes. Therefore, evidence is provided here to confirm that not only BoAHV1 and BuAHV1, but also BoAHV5, can infect water buffaloes. This report highlights (i) the first detection of BoAHV5 in water buffaloes and (ii) the occurrence of coinfections with BoAHV1 and BoAHV5 in that species. Such findings and the similarity of BuAHV1 to Indian herpesvirus genomes suggest that the origin of type 5 may be linked to recombinations between bovine and bubaline herpesviruses within bubalines, since the scenario for generation of recombinants in buffaloes is potentially present. Full article

(This article belongs to the Special Issue Animal Herpesvirus)

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8 pages, 572 KiB

Open AccessCommunication

Bovine Rhinitis B Virus Variant as the Putative Cause of Bronchitis in Goat Kids

by Andrew Noel, Jianqiang Zhang, Huigang Shen, Anugrah Saxena, Jennifer Groeltz-Thrush, Ganwu Li and Michael C. Rahe

Viruses 2024, 16(7), 1023; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071023 - 25 Jun 2024

Viewed by 119

Abstract

A diagnostic investigation into an outbreak of fatal respiratory disease among young goats in Iowa, USA revealed bronchitis lesions of unknown etiology and secondary bacterial bronchopneumonia. Hypothesis-free metagenomics identified a previously unreported picornavirus (USA/IA26017/2023), and further phylogenetic analysis classified USA/IA26017/2023 as an aphthovirus [...] Read more.

A diagnostic investigation into an outbreak of fatal respiratory disease among young goats in Iowa, USA revealed bronchitis lesions of unknown etiology and secondary bacterial bronchopneumonia. Hypothesis-free metagenomics identified a previously unreported picornavirus (USA/IA26017/2023), and further phylogenetic analysis classified USA/IA26017/2023 as an aphthovirus related to bovine rhinitis B virus. Viral nucleic acid was localized to lesions of bronchitis using in situ hybridization. This marks the first report of a picornavirus putatively causing respiratory disease in goats and highlights the potential for cross-species transmission of aphthoviruses. Full article

(This article belongs to the Special Issue Animal Virus Discovery and Genetic Diversity)

14 pages, 2157 KiB

Open AccessArticle

Adapting Real-Time Lung Function Measurements for SARS-CoV-2 Infection Studies in Syrian Hamsters

by Rineke de Jong, Wout Nuiten, Albertjan ter Heide, Wilfred Hamstra, Sandra Vreman, Nadia Oreshkova, Katrin E. Wiese and Nora M. Gerhards

Viruses 2024, 16(7), 1022; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071022 - 25 Jun 2024

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Abstract

Pulmonary function examinations are critical to assess respiratory disease severity in patients. In preclinical rodent models of viral respiratory infections, however, disease is frequently evaluated based on virological, pathological and/or surrogate clinical parameters, which are not directly associated with lung function. To bridge [...] Read more.

Pulmonary function examinations are critical to assess respiratory disease severity in patients. In preclinical rodent models of viral respiratory infections, however, disease is frequently evaluated based on virological, pathological and/or surrogate clinical parameters, which are not directly associated with lung function. To bridge the gap between preclinical and clinical readouts, we aimed to apply unrestrained whole-body plethysmography (WBP) measurements in a SARS-CoV-2 Syrian hamster challenge model. While WBP measurements are frequently used for preclinical research in mice and rats, results from studies in hamsters are still limited. During unrestrained WBP measurements, we obtained highly variable breathing frequency values outside of the normal physiological range for hamsters. Importantly, we observed that animal movements were recorded as breaths during WBP measurements. By limiting animal movement through either mechanical or chemical restraint, we improved the reliability of the lung function readout and obtained breathing frequencies that correlated with clinical signs when comparing two different variants of SARS-CoV-2 post-inoculation. Simultaneously, however, new sources of experimental variation were introduced by the method of restraint, which demands further optimalization of WBP measurements in Syrian hamsters. We concluded that WBP measurements are a valuable refinement either in combination with video recordings or if average values of measurements lasting several hours are analyzed. Full article

(This article belongs to the Special Issue Animal Models for Virology Research)

16 pages, 653 KiB

Open AccessArticle

Prevalence and Symptom Profile of Long COVID among Schoolchildren in Vietnam

by Trang Thu Vu, Khanh Cong Nguyen, Hieu Thi Nguyen, Anh Hoang, Nghia Duy Ngu, Duong Nhu Tran, Hoa Bich Phan, Ha Thi Thu Nguyen, Thai Quang Pham and Florian Vogt

Viruses 2024, 16(7), 1021; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071021 - 25 Jun 2024

Viewed by 174

Abstract

Background: Long COVID is a recognized condition that can follow SARS-CoV-2 infection. It has been primarily observed and studied in adults. Evidence on long COVID among children is scarce. We aimed to estimate its prevalence and symptom profile among schoolchildren, and its effects [...] Read more.

Background: Long COVID is a recognized condition that can follow SARS-CoV-2 infection. It has been primarily observed and studied in adults. Evidence on long COVID among children is scarce. We aimed to estimate its prevalence and symptom profile among schoolchildren, and its effects on studying, daily activities, and quality of life. Methods: We conducted a cross-sectional online survey among caregivers of 2226 schoolchildren aged 12–17 in Thai Nguyen, Vietnam, from 11 April to 16 May 2023 using WHO definitions and a validated quality of life questionnaire. Results: Among 1507 children with confirmed SARS-CoV-2 infection ≥ 5 months prior, 85 (5.6%) had long COVID. Memory loss (85.9%), poor concentration capacity (58.8%), and fatigue (57.6%) were their most common symptoms. They reported more frequent interference with their studies, observed differences in school absence rates, reduced daily activities, worsened overall health status, and relatively higher utilization of health services compared with children who only suffered from acute COVID-19 symptoms after infection. Conclusions: Given the near-ubiquitous exposure to SARS-CoV-2 among children at this stage of the pandemic, our findings contribute invaluable evidence of an emerging public health burden among the pediatric population in Vietnam and globally. Concerted public health measures are needed to reduce long-term impacts on health, education, and wellbeing. Full article

(This article belongs to the Section Coronaviruses)

20 pages, 810 KiB

Open AccessArticle

Diversity of Picorna-Like Viruses in the Teltow Canal, Berlin, Germany

by Roland Zell, Marco Groth, Lukas Selinka and Hans-Christoph Selinka

Viruses 2024, 16(7), 1020; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071020 - 25 Jun 2024

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Abstract

The viromes of freshwater bodies are underexplored. The Picornavirales order, with 371 acknowledged species, is one of the most expansive and diverse groups of eukaryotic RNA viruses. In this study, we add 513 picorna-like viruses to the assemblage of more than 2000 unassigned [...] Read more.

The viromes of freshwater bodies are underexplored. The Picornavirales order, with 371 acknowledged species, is one of the most expansive and diverse groups of eukaryotic RNA viruses. In this study, we add 513 picorna-like viruses to the assemblage of more than 2000 unassigned picorna-like viruses. Our set of the aquatic Picornavirales virome of the Teltow Canal in Berlin, Germany, consists of 239 complete and 274 partial genomes. This urban freshwater body is characterized by the predominance of marna-like viruses (30.8%) and dicistro-like viruses (19.1%), whereas picornaviruses, iflaviruses, solinvi-like viruses, polycipi-like viruses, and nora-like viruses are considerably less prevalent. Caliciviruses and secoviruses were absent in our sample. Although presenting characteristic domains of Picornavirales, more than 100 viruses (20.8%) could not be assigned to any of the 9 Picornavirales families. Thirty-three viruses of the Marnaviridae—mostly locarna-like viruses—exhibit a monocistronic genome layout. Besides a wealth of novel virus sequences, viruses with peculiar features are reported. Among these is a clade of untypeable marna-like viruses with dicistronic genomes, but with the capsid protein-encoding open reading frame located at the 5’ part of their RNA. A virus with a similar genome layout but clustering with dicistroviruses was also observed. We further detected monocistronic viruses with a polymerase gene related to aparaviruses. The detection of Aichi virus and five novel posa-like viruses indicates a slight burden in municipal wastewater. Full article

(This article belongs to the Section General Virology)

11 pages, 741 KiB

Open AccessReview

Local Power: The Role of Tissue-Resident Immunity in Human Genital Herpes Simplex Virus Reactivation

by Jia Zhu and Maurine D. Miner

Viruses 2024, 16(7), 1019; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071019 - 25 Jun 2024

Viewed by 142

Abstract

From established latency, human herpes virus type 2 (HSV-2) frequently reactivates into the genital tract, resulting in symptomatic ulcers or subclinical shedding. Tissue-resident memory (T_RM) CD8+ T cells that accumulate and persist in the genital skin at the local site of [...] Read more.

From established latency, human herpes virus type 2 (HSV-2) frequently reactivates into the genital tract, resulting in symptomatic ulcers or subclinical shedding. Tissue-resident memory (T_RM) CD8+ T cells that accumulate and persist in the genital skin at the local site of recrudescence are the “first responders” to viral reactivation, performing immunosurveillance and containment and aborting the ability of the virus to induce clinical lesions. This review describes the unique spatiotemporal characteristics, transcriptional signatures, and noncatalytic effector functions of T_RM CD8+ T cells in the tissue context of human HSV-2 infection. We highlight recent insights into the intricate overlaps between intrinsic resistance, innate defense, and adaptive immunity in the tissue microenvironment and discuss how rapid virus–host dynamics at the skin and mucosal level influence clinical outcomes of genital herpes diseases. Full article

(This article belongs to the Special Issue Innate and Adaptive Immunity to Cutaneous Virus Infection)

15 pages, 787 KiB

Open AccessArticle

Re-Emergence of Rift Valley Fever Virus Lineage H in Senegal in 2022: In Vitro Characterization and Impact on its Global Emergence in West Africa

by Ousseynou Sene, Samba Niang Sagne, Ndeye Sakha Bob, Moundhir Mhamadi, Idrissa Dieng, Aboubacry Gaye, Haoua Ba, Moussa Dia, Elisabeth Thérèse Faye, Sokhna Mayemouna Diop, Yoro Sall, Boly Diop, Mamadou Ndiaye, Cheikh Loucoubar, Etienne Simon-Lorière, Anavaj Sakuntabhai, Ousmane Faye, Amadou Alpha Sall, Diawo Diallo, Ndongo Dia, Oumar Faye, Moussa Moise Diagne, Malick Fall, Marie Henriette Dior Ndione, Mamadou Aliou Barry and Gamou Fall Show full author list Hide full author list

Viruses 2024, 16(7), 1018; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071018 - 25 Jun 2024

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Abstract

Rift Valley fever (RVF) is a re-emerging vector-borne zoonosis with a high public health and veterinary impact. In West Africa, many lineages were previously detected, but since 2020, lineage H from South Africa has been the main cause of the outbreaks. In this [...] Read more.

Rift Valley fever (RVF) is a re-emerging vector-borne zoonosis with a high public health and veterinary impact. In West Africa, many lineages were previously detected, but since 2020, lineage H from South Africa has been the main cause of the outbreaks. In this study, clinical samples collected through national surveillance were screened for RVF virus (RVFV) acute infection by RT-PCR and IgM ELISA tests. Sequencing, genome mapping and in vitro phenotypic characterization in mammal cells were performed on RT-PCR positive samples in comparison with other epidemic lineages (G and C). Four RVFV human cases were detected in Senegal and the sequence analyses revealed that the strains belonged to lineage H. The in vitro kinetics and genome mapping showed different replication efficiency profiles for the tested RVFV lineages and non-conservative mutations, which were more common to lineage G or specific to lineage H. Our findings showed the re-emergence of lineage H in Senegal in 2022, its high viral replication efficiency in vitro and support the findings that genetic diversity affects viral replication. This study gives new insights into the biological properties of lineage H and calls for deeper studies to better assess its potential to cause a future threat in Senegal. Full article

(This article belongs to the Special Issue Mosquito-Borne Encephalitis Viruses)

12 pages, 868 KiB

Open AccessArticle

Characterization of Herpesviridae Family Members, BK Virus, and Adenovirus in Children and Adolescents with Nephrotic Syndrome

by Silvia Mendonça Ferreira Menoni, Lucas Lopes Leon, Rodrigo Gonçalves de Lima, Anna Cristina Gervásio de Brito Lutaif, Liliane Cury Prates, Lilian Monteiro Pereira Palma, Sandra Cecília Botelho Costa, Vera Maria Santoro Belangero and Sandra Helena Alves Bonon

Viruses 2024, 16(7), 1017; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071017 - 25 Jun 2024

Viewed by 250

Abstract

Since the significance of viral infections in children and adolescents with nephrotic syndrome (NS) is yet to be defined, this study intended to estimate the occurrence, pattern, and outcomes of some DNA viral infections in children with NS. Methods: A prospective study was [...] Read more.

Since the significance of viral infections in children and adolescents with nephrotic syndrome (NS) is yet to be defined, this study intended to estimate the occurrence, pattern, and outcomes of some DNA viral infections in children with NS. Methods: A prospective study was conducted to determine the genome identification of the viruses Epstein-Barr (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6 type A and type B) and 7 (HHV-7), polyomavirus (BKV), and human adenovirus (HAdV) in plasma and urine samples of pediatric patients with NS. Results: A total of 35 patients aged 1 to 18 years with NS and under immunosuppressant drugs participated in the study. Plasma and urine samples were collected at regular intervals during a median follow-up of 266 days (range 133–595), and DNA was analyzed to detect the selected DNA viruses. Eleven patients (31.4%) had active virus infections, and patterns were classified as coinfection, recurrent, and consecutive. Of these, six patients (54.5%) presented viral coinfection, six (54.5%) viral recurrence, and seven patients (63.3%) had viral consecutive infection. Ten of the eleven patients with active infection had a proteinuria relapse (91%) and eight (72.7%) were hospitalized (p = 0.0022). Active HCMV infection was the most frequent infection and was observed in six patients (54.5%), three of the eleven patients (27.2%) had suspected HCMV disease in the gastrointestinal tract, and one had HHV-7 coinfection. The frequency of other infections was: 9% for HHV-6, 45.5% for BKV, 27.3% for HHV-7, 18.2% for EBV, and 18.2% for HAdV. Conclusion: viral infections, especially HCMV, can be an important cause of morbidity and nephrotic syndrome relapse in children. Full article

(This article belongs to the Special Issue Opportunistic Viral Infections 2nd Edition)

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19 pages, 1569 KiB

Open AccessArticle

Development of Dry and Liquid Duplex Reagent Mix-Based Polymerase Chain Reaction Assays as Novel Tools for the Rapid and Easy Quantification of Bovine Leukemia Virus (BLV) Proviral Loads

by Sonoko Watanuki, Kazuyuki Shoji, Masaki Izawa, Mitsuaki Okami, Yingbao Ye, Aronggaowa Bao, Yulin Liu, Etsuko Saitou, Kimikazu Sugiyama, Michiru Endo, Yasunobu Matsumoto and Yoko Aida

Viruses 2024, 16(7), 1016; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071016 - 25 Jun 2024

Viewed by 181

Abstract

Bovine leukemia virus (BLV) is prevalent worldwide, causing serious problems in the cattle industry. The BLV proviral load (PVL) is a useful index for estimating disease progression and transmission risk. We previously developed a quantitative real-time PCR (qPCR) assay to measure the PVL [...] Read more.

Bovine leukemia virus (BLV) is prevalent worldwide, causing serious problems in the cattle industry. The BLV proviral load (PVL) is a useful index for estimating disease progression and transmission risk. We previously developed a quantitative real-time PCR (qPCR) assay to measure the PVL using the coordination of common motif (CoCoMo) degenerate primers. Here, we constructed a novel duplex BLV-CoCoMo qPCR assay that can amplify two genes simultaneously using a FAM-labeled MGB probe for the BLV LTR gene and a VIC-labeled MGB probe for the BoLA-DRA gene. This liquid duplex assay maintained its original sensitivity and reproducibility in field samples. Furthermore, we developed a dry duplex assay composed of PCR reagents necessary for the optimized liquid duplex assay. We observed a strong positive correlation between the PVLs measured using the dry and liquid duplex assays. Validation analyses showed that the sensitivity of the dry duplex assay was slightly lower than that of the other methods for the detection of a BLV molecular clone, but it showed similar sensitivity to the singleplex assay and slightly higher sensitivity than the liquid duplex assay for the PVL quantification of 82 field samples. Thus, our liquid and dry duplex assays are useful for measuring the BLV PVL in field samples, similar to the original singleplex assay. Full article

(This article belongs to the Section Animal Viruses)

14 pages, 1735 KiB

Open AccessArticle

Prevalence and Genetic Diversity of Bat Hepatitis B Viruses in Bat Species Living in Gabon

by Danielle S. Koumba Mavoungou, Linda Bohou Kombila, Neil M. Longo Pendy, Schedy E. Koumba Moukouama, Sonia Etenna Lekana-Douki, Gaël D. Maganga, Eric M. Leroy, Avelin F. Aghokeng and Nadine N’dilimabaka

Viruses 2024, 16(7), 1015; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071015 - 25 Jun 2024

Viewed by 222

Abstract

Hepatitis B virus (HBV) infection leads to around 800,000 deaths yearly and is considered to be a major public health problem worldwide. However, HBV origins remain poorly understood. Here, we looked for bat HBV (BtHBV) in different bat species in Gabon to investigate [...] Read more.

Hepatitis B virus (HBV) infection leads to around 800,000 deaths yearly and is considered to be a major public health problem worldwide. However, HBV origins remain poorly understood. Here, we looked for bat HBV (BtHBV) in different bat species in Gabon to investigate the role of these animals as carriers of ancestral hepadnaviruses because these viruses are much more diverse in bats than in other host species. DNA was extracted from 859 bat livers belonging to 11 species collected in caves and villages in the southeast of Gabon and analyzed using PCRs targeting the surface gene. Positive samples were sequenced using the Sanger method. BtHBV DNA was detected in 64 (7.4%) individuals belonging to eight species mainly collected in caves. Thirty-six (36) sequences among the 37 obtained after sequencing were phylogenetically close to the RBHBV strain recently isolated in Gabonese bats, while the remaining sequence was close to a rodent HBV strain isolated in America. The generalized linear mixed model showed that the variable species best explained the occurrence of BtHBV infection in bats. The discovery of a BtHBV strain homologous to a rodent strain in bats raises the possibility that these animals may be carriers of ancestral hepadnaviruses. Full article

(This article belongs to the Section Animal Viruses)

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15 pages, 2607 KiB

Open AccessArticle

Viral Envelope Evolution in Simian–HIV-Infected Neonate and Adult-Dam Pairs of Rhesus Macaques

by Elena E. Giorgi, Hui Li, Bhavna Hora, George M. Shaw, Kshitij Wagh and Wilton B. Williams

Viruses 2024, 16(7), 1014; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071014 - 25 Jun 2024

Viewed by 155

Abstract

We recently demonstrated that Simian–HIV (SHIV)-infected neonate rhesus macaques (RMs) generated heterologous HIV-1 neutralizing antibodies (NAbs) with broadly-NAb (bNAb) characteristics at a higher frequency compared with their corresponding dam. Here, we characterized genetic diversity in Env sequences from four neonate or adult/dam RM [...] Read more.

We recently demonstrated that Simian–HIV (SHIV)-infected neonate rhesus macaques (RMs) generated heterologous HIV-1 neutralizing antibodies (NAbs) with broadly-NAb (bNAb) characteristics at a higher frequency compared with their corresponding dam. Here, we characterized genetic diversity in Env sequences from four neonate or adult/dam RM pairs: in two pairs, neonate and dam RMs made heterologous HIV-1 NAbs; in one pair, neither the neonate nor the dam made heterologous HIV-1 NAbs; and in another pair, only the neonate made heterologous HIV-1 NAbs. Phylogenetic and sequence diversity analyses of longitudinal Envs revealed that a higher genetic diversity, within the host and away from the infecting SHIV strain, was correlated with heterologous HIV-1 NAb development. We identified 22 Env variable sites, of which 9 were associated with heterologous HIV-1 NAb development; 3/9 sites had mutations previously linked to HIV-1 Env bNAb development. These data suggested that viral diversity drives heterologous HIV-1 NAb development, and the faster accumulation of viral diversity in neonate RMs may be a potential mechanism underlying bNAb induction in pediatric populations. Moreover, these data may inform candidate Env immunogens to guide precursor B cells to bNAb status via vaccination by the Env-based selection of bNAb lineage members with the appropriate mutations associated with neutralization breadth. Full article

(This article belongs to the Special Issue Simian Immunodeficiency Virus Models of HIV/AIDS in Nonhuman Primates 2024)

12 pages, 1655 KiB

Open AccessArticle

Molecular Genotyping of Circulating Enterovirus in the Lazio Region from 2012 to 2023

by Martina Rueca, Francesco Vairo, Martina Spaziante, Lavinia Fabeni, Federica Forbici, Giulia Berno, Cesare Ernesto Maria Gruber, Simonetta Picone, Camilla Ajassa, Enrico Girardi, Fabrizio Maggi and Maria Beatrice Valli

Viruses 2024, 16(7), 1013; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071013 - 24 Jun 2024

Viewed by 199

Abstract

Enteroviruses (EVs) are ubiquitous viruses that circulate worldwide, causing sporadic or epidemic infections, typically during the summer and fall. They cause a broad spectrum of illnesses, ranging from an unspecified febrile clinical presentation to a severe illness. EVs are recognized to be the [...] Read more.

Enteroviruses (EVs) are ubiquitous viruses that circulate worldwide, causing sporadic or epidemic infections, typically during the summer and fall. They cause a broad spectrum of illnesses, ranging from an unspecified febrile clinical presentation to a severe illness. EVs are recognized to be the most frequent etiological agents of aseptic meningitis in children. However, as the infection is usually mild and self-limiting, it remains underestimated, and the epidemiology of EVs is poorly understood. To date, no vaccine or effective therapy for all types of enteroviruses is available, and EVs constitute a public health concern. Here, we investigated the molecular epidemiology of EV strains circulating in the Lazio region over a 10-year time span (2012–2023) by using a sequence-typing approach and phylogenetic analysis. The epidemiological trend of EV infection has undergone changes during the SARS-CoV-2 pandemic (2020–2021), which resulted in a modification in terms of the number of diagnosed cases and seasonality. From 2022, the circulation of EVs showed a behavior typical of the pre-pandemic period, although changes in predominantly circulating strains have been noted. Both epidemic and sporadic circulation events have been characterized in the Lazio region. Further analyses are needed to better characterize any strain with higher potential pathogenic power and to identify possible recombinant strains. Full article

(This article belongs to the Special Issue Virology in Italy 2023: National Congress of the Italian Society for Virology)

18 pages, 924 KiB

Open AccessArticle

Immunogenetic Profile Associated with Patients Living with HIV-1 and Epstein–Barr Virus (EBV) in the Brazilian Amazon Region

by Iran Barros Costa, Mayara Natália Santana-da-Silva, Patrícia Yuri Nogami, Carolinne de Jesus Santos e Santos, Leonn Mendes Soares Pereira, Eliane dos Santos França, Amaury Bentes Cunha Freire, Francisco Lúzio de Paula Ramos, Talita Antonia Furtado Monteiro, Olinda Macedo, Rita Catarina Medeiros Sousa, Felipe Bonfim Freitas, Antonio Carlos Rosário Vallinoto and Igor Brasil-Costa

Viruses 2024, 16(7), 1012; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071012 - 24 Jun 2024

Viewed by 178

Abstract

Viral coinfection among HIV-positive patients, coupled with the development of AIDS, remains a major public health problem. The synergism between the presence of HIV and other viruses has consequences in relation to changes in the severity of the infection, as well as changes [...] Read more.

Viral coinfection among HIV-positive patients, coupled with the development of AIDS, remains a major public health problem. The synergism between the presence of HIV and other viruses has consequences in relation to changes in the severity of the infection, as well as changes in the natural course of both infections. Several polymorphisms present in genes that encode cytokines have a relevant influence on their transcription and consequently on the production of such immunological molecules. The present study evaluated the influence of SNPs located in the promoter regions of genes encoding the cytokines INF-ɣ, TNF, IL-6, IL-4, and IL-2, as well as their respective plasma concentrations, in patients infected with HIV and/or EBV in the state of Pará. Additionally, this study described the epidemiological profile and compared CD4+ and CD8+ T lymphocyte counts among the groups studied. The associative analysis between the SNPs and plasma cytokine concentrations in different groups showed statistical relevance for three polymorphisms: rs2069762 (IL2), where the GG genotype demonstrated higher IL-2 levels in HIV mono-infected individuals; rs2243250 (IL4), where the CT genotype showed higher IL-4 levels in the control group; and rs2069705 (IFNG), where the TT genotype showed higher IFN-γ levels in the coinfected group. Regarding SNP associations with CD4+/CD8+ counts, significant findings were observed in HIV mono-infected individuals: the rs2069705 (IFNG) polymorphism was linked to higher CD4+ counts with the CT genotype, and rs1799964 (TNF) was associated with higher CD8+ counts with the CC genotype. Therefore, this study provides evidence that the rs2069705 (IFNG) SNP is associated with elevated IFN-γ levels, which may have pathogenic consequences, as depletion of this cytokine is concerning for people living with HIV due to its antiviral properties. Full article

(This article belongs to the Special Issue HIV and HTLV Infections and Coinfections)

16 pages, 2366 KiB

Open AccessArticle

Intensified Circulation of Echovirus 11 after the COVID-19 Pandemic in Poland: Detection of a Highly Pathogenic Virus Variant

by Beata Gad, Paulina Kłosiewicz, Kinga Oleksiak, Arleta Krzysztoszek, Kacper Toczyłowski, Artur Sulik, Tobiasz Wieczorek and Magdalena Wieczorek

Viruses 2024, 16(7), 1011; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071011 - 24 Jun 2024

Viewed by 413

Abstract

After the first phase of the COVID-19 pandemic in Europe, a new highly pathogenic variant of echovirus 11 (E11) was detected. The aim of this study was to analyze the genetic diversity of Polish E11 environmental and clinical strains circulating between 2017 and [...] Read more.

After the first phase of the COVID-19 pandemic in Europe, a new highly pathogenic variant of echovirus 11 (E11) was detected. The aim of this study was to analyze the genetic diversity of Polish E11 environmental and clinical strains circulating between 2017 and 2023 as well as compare them with E11 strains isolated from severe neonatal sepsis cases reported in Europe between 2022 and 2023. Additionally, the study explores the effectiveness of environmental monitoring in tracking the spread of new variants. For this purpose, the complete sequences of the VP1 capsid protein gene were determined for 266 E11 strains isolated in Poland from 2017 to 2023, and phylogenetic analysis was performed. In the years 2017–2023, a significant increase in the detection of E11 strains was observed in both environmental and clinical samples in Poland. The Polish E11 strains represented three different genotypes, C3, D5 and E, and were characterized by a high diversity. In Poland, the intensive circulation of the new variant E11, responsible for severe neonatal infections with a high mortality in Europe, was detected in the years 2022–2023. This investigation demonstrates the important role of environmental surveillance in the tracking of enteroviruses circulation, especially in settings with limited clinical surveillance. Full article

(This article belongs to the Special Issue An Update on Enterovirus Research)

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17 pages, 1283 KiB

Open AccessArticle

Progress in Early Detection of HIV in Tajikistan

by Kamiar Alaei, Brian Kwan, Hamid R. Torabzadeh, Adebimpe O. Akinwalere, Sattorov S. Saydamirovich, Gafur Mohsinzoda and Arash Alaei

Viruses 2024, 16(7), 1010; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071010 - 23 Jun 2024

Viewed by 295

Abstract

HIV early detection (CD4 counts ≥ 350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors, including physical, cultural, structural, and financial barriers, may limit early detection of HIV. This is a first-of-its-kind study on population-level differences [...] Read more.

HIV early detection (CD4 counts ≥ 350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors, including physical, cultural, structural, and financial barriers, may limit early detection of HIV. This is a first-of-its-kind study on population-level differences in early detection of HIV across time within Tajikistan and any country in the Central Asia region. Utilizing the Tajikistan Ministry of Health’s national HIV data (N = 10,700) spanning 2010 to 2023, we developed median regression models with the median CD4 cell count as the outcome and with the following predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old were detected early for HIV, whereas those older than 39 years were detected late. Females were detected earlier compared to their male counterparts regardless of region of residence. Rural populations were detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. There were differences identified among different demographic and geographic groups which warrant further attention. Full article

(This article belongs to the Special Issue HIV Elimination as the Goal by 2030 - 2nd Edition)

24 pages, 8562 KiB

Open AccessArticle

Exploration of Potential Broad-Spectrum Antiviral Targets in the Enterovirus Replication Element: Identification of Six Distinct 5′ Cloverleaves

by Morgan G. Daniels, Meagan E. Werner, Rockwell T. Li and Steven M. Pascal

Viruses 2024, 16(7), 1009; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071009 - 23 Jun 2024

Viewed by 253

Abstract

Enterovirus genomic replication initiates at a predicted RNA cloverleaf (5′CL) at the 5′ end of the RNA genome. The 5′CL contains one stem (SA) and three stem-loops (SLB, SLC, SLD). Here, we present an analysis of 5′CL conservation and divergence for 209 human [...] Read more.

Enterovirus genomic replication initiates at a predicted RNA cloverleaf (5′CL) at the 5′ end of the RNA genome. The 5′CL contains one stem (SA) and three stem-loops (SLB, SLC, SLD). Here, we present an analysis of 5′CL conservation and divergence for 209 human health-related serotypes from the enterovirus genus, including enterovirus and rhinovirus species. Phylogenetic analysis indicates six distinct 5′CL serotypes that only partially correlate with the species definition. Additional findings include that 5′CL sequence conservation is higher between the EV species than between the RV species, the 5′CL of EVA and EVB are nearly identical, and RVC has the lowest 5′CL conservation. Regions of high conservation throughout all species include SA and the loop and nearby bases of SLB, which is consistent with known protein interactions at these sites. In addition to the known protein binding site for the Poly-C binding protein in the loop of SLB, other conserved consecutive cytosines in the stems of SLB and SLC provide additional potential interaction sites that have not yet been explored. Other sites of conservation, including the predicted bulge of SLD and other conserved stem, loop, and junction regions, are more difficult to explain and suggest additional interactions or structural requirements that are not yet fully understood. This more intricate understanding of sequence and structure conservation and variability in the 5′CL may assist in the development of broad-spectrum antivirals against a wide range of enteroviruses, while better defining the range of virus isotypes expected to be affected by a particular antiviral. Full article

(This article belongs to the Special Issue An Update on Enterovirus Research)

16 pages, 7293 KiB

Open AccessArticle

SARS-CoV-2 Accessory Protein ORF8 Targets the Dimeric IgA Receptor pIgR

by Frederique Laprise, Ariana Arduini, Mathew Duguay, Qinghua Pan and Chen Liang

Viruses 2024, 16(7), 1008; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071008 - 22 Jun 2024

Viewed by 377

Abstract

SARS-CoV-2 is a highly pathogenic respiratory virus that successfully initiates and establishes its infection at the respiratory mucosa. However, little is known about how SARS-CoV-2 antagonizes the host’s mucosal immunity. Recent findings have shown a marked reduction in the expression of the polymeric [...] Read more.

SARS-CoV-2 is a highly pathogenic respiratory virus that successfully initiates and establishes its infection at the respiratory mucosa. However, little is known about how SARS-CoV-2 antagonizes the host’s mucosal immunity. Recent findings have shown a marked reduction in the expression of the polymeric Ig receptor (pIgR) in COVID-19 patients. This receptor maintains mucosal homeostasis by transporting the dimeric IgA (dIgA) and pentameric IgM (pIgM) across mucosal epithelial cells to neutralize the invading respiratory pathogens. By studying the interaction between pIgR and SARS-CoV-2 proteins, we discovered that the viral accessory protein Open Reading Frame 8 (ORF8) potently downregulates pIgR expression and that this downregulation activity of ORF8 correlates with its ability to interact with pIgR. Importantly, the ORF8-mediated downregulation of pIgR diminishes the binding of dIgA or pIgM, and the ORF8 proteins of the variants of concern of SARS-CoV-2 preserve the function of downregulating pIgR, indicating the importance of this conserved activity of ORF8 in SARS-CoV-2 pathogenesis. We further observed that the secreted ORF8 binds to cell surface pIgR, but that this interaction does not trigger the cellular internalization of ORF8, which requires the binding of dIgA to pIgR. These findings suggest the role of ORF8 in SARS-CoV-2 mucosal immune evasion. Full article

(This article belongs to the Special Issue Coronaviruses Pathogenesis, Immunity, and Antivirals)

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20 pages, 1082 KiB

Open AccessReview

Engineered Resistance to Tobamoviruses

by John Peter Carr

Viruses 2024, 16(7), 1007; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071007 - 22 Jun 2024

Viewed by 491

Abstract

Tobacco mosaic virus (TMV) was the first virus to be studied in detail and, for many years, TMV and other tobamoviruses, particularly tomato mosaic virus (ToMV) and tobamoviruses infecting pepper (Capsicum spp.), were serious crop pathogens. By the end of the twentieth [...] Read more.

Tobacco mosaic virus (TMV) was the first virus to be studied in detail and, for many years, TMV and other tobamoviruses, particularly tomato mosaic virus (ToMV) and tobamoviruses infecting pepper (Capsicum spp.), were serious crop pathogens. By the end of the twentieth and for the first decade of the twenty-first century, tobamoviruses were under some degree of control due to introgression of resistance genes into commercial tomato and pepper lines. However, tobamoviruses remained important models for molecular biology, biotechnology and bio-nanotechnology. Recently, tobamoviruses have again become serious crop pathogens due to the advent of tomato brown rugose fruit virus, which overcomes tomato resistance against TMV and ToMV, and the slow but apparently inexorable worldwide spread of cucumber green mottle mosaic virus, which threatens all cucurbit crops. This review discusses a range of mainly molecular biology-based approaches for protecting crops against tobamoviruses. These include cross-protection (using mild tobamovirus strains to ‘immunize’ plants against severe strains), expressing viral gene products in transgenic plants to inhibit the viral infection cycle, inducing RNA silencing against tobamoviruses by expressing virus-derived RNA sequences in planta or by direct application of double-stranded RNA molecules to non-engineered plants, gene editing of host susceptibility factors, and the transfer and optimization of natural resistance genes. Full article

(This article belongs to the Special Issue Tobamoviruses: Molecular Aspects and Resistance Regulation—a Special Issue Commemorating 125 Years of Research on Tobamoviruses)

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21 pages, 658 KiB

Open AccessArticle

T-Cell Epitope Mapping of SARS-CoV-2 Reveals Coordinated IFN-γ Production and Clonal Expansion of T Cells Facilitates Recovery from COVID-19

by Xing Fan, Jin-wen Song, Wen-jing Cao, Ming-ju Zhou, Tao Yang, Jing Wang, Fan-ping Meng, Ming Shi, Chao Zhang and Fu-sheng Wang

Viruses 2024, 16(7), 1006; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071006 - 22 Jun 2024

Viewed by 281

Abstract

Background: T-cell responses can be protective or detrimental during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, the underlying mechanism is poorly understood. Methods: In this study, we screened 144 15-mer peptides spanning the SARS-CoV-2 spike, nucleocapsid (NP), M, ORF8, ORF10, [...] Read more.

Background: T-cell responses can be protective or detrimental during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, the underlying mechanism is poorly understood. Methods: In this study, we screened 144 15-mer peptides spanning the SARS-CoV-2 spike, nucleocapsid (NP), M, ORF8, ORF10, and ORF3a proteins and 39 reported SARS-CoV-1 peptides in peripheral blood mononuclear cells (PBMCs) from nine laboratory-confirmed coronavirus disease 2019 (COVID-19) patients (five moderate and four severe cases) and nine healthy donors (HDs) collected before the COVID-19 pandemic. T-cell responses were monitored by IFN-γ and IL-17A production using ELISA, and the positive samples were sequenced for the T cell receptor (TCR) β chain. The positive T-cell responses to individual SARS-CoV-2 peptides were validated by flow cytometry. Results: COVID-19 patients with moderate disease produced more IFN-γ than HDs and patients with severe disease (moderate vs. HDs, p < 0.0001; moderate vs. severe, p < 0.0001) but less IL-17A than those with severe disease (p < 0.0001). A positive correlation was observed between IFN-γ production and T-cell clonal expansion in patients with moderate COVID-19 (r = 0.3370, p = 0.0214) but not in those with severe COVID-19 (r = −0.1700, p = 0.2480). Using flow cytometry, we identified that a conserved peptide of the M protein (Peptide-120, P120) was a dominant epitope recognized by CD8+ T cells in patients with moderate disease. Conclusion: Coordinated IFN-γ production and clonal expansion of SARS-CoV-2-specific T cells are associated with disease resolution in COVID-19. Our findings contribute to a better understanding of T-cell-mediated immunity in COVID-19 and may inform future strategies for managing and preventing severe outcomes of SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue Coronaviruses Pathogenesis, Immunity, and Antivirals)

11 pages, 526 KiB

Open AccessArticle

Mismanagement of SARS-CoV-2 Infection Pre Hospitalisation during the Omicron Era: Antibiotics and Steroids Instead of Early Antivirals

by Andrea Giacomelli, Cosmin Lucian Ciubotariu, Martina Zacheo, Andrea Rabbione, Margherita Pieruzzi, Federico Barone, Andrea Poloni, Giacomo Casalini, Giacomo Pozza, Marta Colaneri, Matteo Passerini, Anna Lisa Ridolfo, Cristina Gervasoni, Dario Cattaneo, Andrea Gori and Spinello Antinori

Viruses 2024, 16(7), 1005; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071005 - 22 Jun 2024

Viewed by 242

Abstract

The aim of this study was to assess the prevalence of inappropriate treatment among hospitalised patients affected by SARS-CoV-2 infection before hospital admission during the Omicron era. This single-centre, retrospective observational study included all the patients hospitalised because of SARS-CoV-2 infection during three [...] Read more.

The aim of this study was to assess the prevalence of inappropriate treatment among hospitalised patients affected by SARS-CoV-2 infection before hospital admission during the Omicron era. This single-centre, retrospective observational study included all the patients hospitalised because of SARS-CoV-2 infection during three periods characterised by the Italian prevalence of an Omicron variant of concern: (1) January–May 2022 (BA.1–BA.2), (2) June–October 2022 (BA.5), and (3) November 2022–March 2023 (BQ.1-XBB). Inappropriate treatment was defined as pre-hospitalisation exposure to antibiotics and/or steroids in the absence of a documented bacterial infection or the need for steroid treatment of an underlying medical condition. A total of 931 subjects were hospitalised: 394 in period 1, 334 in period 2, and 203 in period 3. Of the 157 patients undergoing inappropriate treatment (16.9%), 142 (15.3%) received antibiotics and 52 (5.6%) steroids. The proportion of inappropriately treated patients significantly decreased over time, from 23.1% in period 1 to 11.7% in period 2 and 13.3% in period 3 (p < 0.001), and there was a parallel decrease in antibiotic (p < 0.001) and steroid treatment (p < 0.013). Only 13 subjects (1.4%) received early pre-hospitalisation treatment for SARS-CoV-2. A significant proportion of hospitalised COVID-19 patients were exposed to inappropriate treatment before hospital admission. Full article

(This article belongs to the Section Coronaviruses)

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18 pages, 443 KiB

Open AccessReview

Macrophage Activation Syndrome in Viral Sepsis

by Despoina Papageorgiou, Charalambos Gogos and Karolina Akinosoglou

Viruses 2024, 16(7), 1004; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071004 - 22 Jun 2024

Viewed by 320

Abstract

Macrophage activation syndrome (MAS) is a life-threatening systemic hyperinflammatory syndrome triggered by various infections, particularly viral infections, autoimmune disorders, and malignancy. The condition is characterized by an increased production of proinflammatory cytokines resulting in a cytokine storm and has been associated with poor [...] Read more.

Macrophage activation syndrome (MAS) is a life-threatening systemic hyperinflammatory syndrome triggered by various infections, particularly viral infections, autoimmune disorders, and malignancy. The condition is characterized by an increased production of proinflammatory cytokines resulting in a cytokine storm and has been associated with poor clinical outcomes. During the COVID-19 pandemic, patients with severe manifestations developed features similar to those of MAS, although these characteristics remained well defined within the lung. Additionally, other viral infections including EBV, the herpes family of viruses, hepatitis viruses, influenza, HIV, and hemorrhagic fevers can be complicated by MAS. The diagnosis and management of the condition remain challenging due to the lack of consensus on specific guidelines, especially among the adult population. Currently, therapeutic options primarily rely on medications that are typically used to treat primary hemophagocytic lymphohistiocytosis, such as corticosteroids and etoposide. In addition, cytokine-targeted therapies present promising treatment options. The objective of this review is to discuss the emergence of MAS in the context of viral infections including, but not limited to, its occurrence in COVID-19. Full article

(This article belongs to the Special Issue Viral Sepsis: Pathogenesis, Diagnostics and Therapeutics)

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12 pages, 2762 KiB

Open AccessArticle

Association between Sleep and Language Development in Children with Congenital Zika Syndrome

by Nathani C. da Silva, Celia M. Giacheti, Maria C. H. do Couto, Stefany S. de Jesus, Erlane M. Ribeiro, Islane M. C. Verçosa and Luciana Pinato

Viruses 2024, 16(7), 1003; https://0-doi-org.brum.beds.ac.uk/10.3390/v16071003 - 22 Jun 2024

Viewed by 210

Abstract

AIM: Congenital Zika Virus Syndrome (CZS) presents notable hurdles to neurodevelopment, with language development emerging as a crucial aspect. This study investigates sleep patterns and language skills in children with CZS, aiming to explore the potential synchronization of sleep development with their neurodevelopment. [...] Read more.

AIM: Congenital Zika Virus Syndrome (CZS) presents notable hurdles to neurodevelopment, with language development emerging as a crucial aspect. This study investigates sleep patterns and language skills in children with CZS, aiming to explore the potential synchronization of sleep development with their neurodevelopment. METHOD: We studied cross-sectionally 135 children with CZS aged 0 to 48 months, investigating sleep using the BISQ Questionnaire. Language development was assessed using the Early Language Milestone Scale, while motor development and cognitive and social ability were assessed using the Bayley Scales of Infant and Young Child Development 3rd edition. We also studied longitudinally a cohort of 16 children (initially aged 0 to 12 months) whom we followed for four years, assessing at one-year intervals. RESULTS: Sleep disturbances and language deficits were highly frequent in this population. In the 0–12 months group, a late bedtime and frequent nighttime awakenings were associated with poorer auditory expressive skills. At 13–24 months, nighttime awakenings were associated with poorer auditory expressive skills, while among 25–36-month-olds decreased auditory receptive skills were associated with longer sleep onset latency and reduced nighttime sleep duration. CONCLUSION: The brain alterations caused by Zika virus infection affect both sleep disturbances and delays in language development. It is possible that sleep disturbance may be a mediating factor in the pathway between CZS and delayed language development, as the three analyzed language skills showed a correlation with sleep parameters. Full article

(This article belongs to the Special Issue Zika Virus and Congenital Zika Syndrome)

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Open AccessArticle

Distinct Pathological Changes in Preweaning Mice Infected with Live-Attenuated Rift Valley Fever Virus Strains

by Cigdem Alkan, Eduardo Jurado-Cobena and Tetsuro Ikegami

Viruses 2024, 16(7), 999; https://0-doi-org.brum.beds.ac.uk/10.3390/v16070999 - 21 Jun 2024

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Abstract

Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Middle East. Live-attenuated RVF vaccines have been studied for both veterinary and human use due to their strong immunogenicity and cost-effective manufacturing. The live-attenuated MP-12 vaccine has been [...] Read more.

Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Middle East. Live-attenuated RVF vaccines have been studied for both veterinary and human use due to their strong immunogenicity and cost-effective manufacturing. The live-attenuated MP-12 vaccine has been conditionally approved for veterinary use in the U.S.A., and next-generation live-attenuated RVF vaccine candidates are being actively researched. Assessing the virulence phenotype of vaccine seeds or lots is crucial for managing vaccine safety. Previously, preweaning 19-day-old outbred CD1 mice have been used to evaluate the MP-12 strain. This study aimed to characterize the relative virulence of three live-attenuated RVF vaccine strains in 19-day-old inbred C57BL/6 mice: the recombinant MP-12 (rMP-12), the RVax-1, and the ∆NSs-∆NSm-rZH501 strains. Although this mouse model did not show dose-dependent pathogenesis, mice that succumbed to the infection exhibited distinct brain pathology. Mice infected with ∆NSs-∆NSm-rZH501 showed an infiltration of inflammatory cells associated with infected neurons, and focal lesions formed around virus-infected cells. In contrast, mice infected with rMP-12 or RVax-1 showed a minimal association of inflammatory cells in the brain, yet the virus spread diffusely. The preweaning model is likely useful for evaluating host responses to attenuated RVFV strains, although further refinement may be necessary to quantitate the virulence among different RVFV strains or vaccine lots. Full article

(This article belongs to the Special Issue Emerging Highlights in the Study of Rift Valley Fever Virus)

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Viruses, Volume 16, Issue 7 (July 2024) – 35 articles

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