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Viruses, Volume 13, Issue 9 (September 2021) – 214 articles

Cover Story (view full-size image): Cell-to-cell spread is an important mechanism of herpesvirus for their dissemination and to evade the host immune response. The molecular tweezer, CLR01, exhibits broad-spectrum antiviral activity against enveloped viruses, which is based on its affinity for viral envelopes and their rapid disruption. CLR01 not only inhibits infection by cell-free viruses but also prevents cell-to-cell spread of herpesviruses, providing valuable mechanistic insights. Furthermore, it marks the viral envelope as an interesting and promising target for future drug development. View this paper.
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Review
COVID-19: Mechanistic Model of the African Paradox Supports the Central Role of the NF-κB Pathway
Viruses 2021, 13(9), 1887; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091887 - 21 Sep 2021
Viewed by 692
Abstract
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has expanded into a global pandemic, with more than 220 million affected persons and almost 4.6 million deaths by 8 September 2021. In particular, Europe and the Americas have been heavily affected by high [...] Read more.
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has expanded into a global pandemic, with more than 220 million affected persons and almost 4.6 million deaths by 8 September 2021. In particular, Europe and the Americas have been heavily affected by high infection and death rates. In contrast, much lower infection rates and mortality have been reported generally in Africa, particularly in the sub-Saharan region (with the exception of the Southern Africa region). There are different hypotheses for this African paradox, including less testing, the young age of the population, genetic disposition, and behavioral and epidemiological factors. In the present review, we address different immunological factors and their correlation with genetic factors, pre-existing immune status, and differences in cytokine induction patterns. We also focus on epidemiological factors, such as specific medication coverage, helminth distribution, and malaria endemics in the sub-Saharan region. An analysis combining different factors is presented that highlights the central role of the NF-κB signaling pathway in the African paradox. Importantly, insights into the interplay of different factors with the underlying immune pathological mechanisms for COVID-19 can provide a better understanding of the disease and the development of new targets for more efficient treatment strategies. Full article
(This article belongs to the Special Issue Host Targeted Therapeutics against Virus Infections)
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Article
Molecular Basis of Antigenic Drift in Serotype O Foot-and-Mouth Disease Viruses (2013–2018) from Southeast Asia
Viruses 2021, 13(9), 1886; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091886 - 21 Sep 2021
Viewed by 480
Abstract
Foot and mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals with serious economic consequences. FMD is endemic in Southeast Asia (SEA) and East Asia (EA) with the circulation of multiple serotypes, posing a threat to Australia and other FMD-free countries. [...] Read more.
Foot and mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals with serious economic consequences. FMD is endemic in Southeast Asia (SEA) and East Asia (EA) with the circulation of multiple serotypes, posing a threat to Australia and other FMD-free countries. Although vaccination is one of the most important control measures to prevent FMD outbreaks, the available vaccines may not be able to provide enough cross-protection against the FMD viruses (FMDVs) circulating in these countries due to the incursion of new lineages and sub-lineages as experienced in South Korea during 2010, a FMD-free country, when a new lineage of serotype O FMDV (Mya-98) spread to the country, resulting in devastating economic consequences. In this study, a total of 62 serotype O (2013–2018) viruses selected from SEA and EA countries were antigenically characterized by virus neutralization tests using three existing (O/HKN/6/83, O/IND/R2/75 and O/PanAsia-2) and one putative (O/MYA/2009) vaccine strains and full capsid sequencing. The Capsid sequence analysis revealed three topotypes, Cathay, SEA and Middle East-South Asia (ME-SA) of FMDVs circulating in the region. The vaccines used in this study showed a good match with the SEA and ME-SA viruses. However, none of the recently circulating Cathay topotype viruses were protected by any of the vaccine strains, including the existing Cathay topotype vaccine (O/HKN/6/83), indicating an antigenic drift and, also the urgency to monitor this topotype in the region and develop a new vaccine strain if necessary, although currently the presence of this topotype is mainly restricted to China, Hong Kong, Taiwan and Vietnam. Further, the capsid sequences of these viruses were analyzed that identified several capsid amino acid substitutions involving neutralizing antigenic sites 1, 2 and 5, which either individually or together could underpin the observed antigenic drift. Full article
(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)
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Review
Potential Diagnostic and Prognostic Biomarkers for Adenovirus Respiratory Infection in Children and Young Adults
Viruses 2021, 13(9), 1885; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091885 - 21 Sep 2021
Viewed by 358
Abstract
Human Adenoviruses (HAdV) are known to be potentially associated with strong inflammatory responses and morbidity in pediatric patients. Although most of the primary infections are self-limiting, the severity of clinical presentation, the elevation of the white blood cell count and inflammatory markers often [...] Read more.
Human Adenoviruses (HAdV) are known to be potentially associated with strong inflammatory responses and morbidity in pediatric patients. Although most of the primary infections are self-limiting, the severity of clinical presentation, the elevation of the white blood cell count and inflammatory markers often mimic a bacterial infection and lead to an inappropriate use of antibiotics. In infections caused by HAdV, rapid antigen detection kits are advisable but not employed routinely; costs and feasibility of rapid syndromic molecular diagnosis may limit its use in the in-hospital setting; lymphocyte cultures and two-sampled serology are time consuming and impractical when considering the use of antibiotics. In this review, we aim to describe the principal diagnostic tools and the immune response in HAdV infections and evaluate whether markers based on the response of the host may help early recognition of HAdV and avoid inappropriate antimicrobial prescriptions in acute airway infections. Full article
(This article belongs to the Special Issue State-of-the-Art Emerging Respiratory Viruses in Europe)
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Article
COVID-19 Infection in Pregnancy: PCR Cycle Thresholds, Placental Pathology, and Perinatal Outcomes
Viruses 2021, 13(9), 1884; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091884 - 21 Sep 2021
Viewed by 1023
Abstract
(1) This study aimed to evaluate characteristics, perinatal outcomes, and placental pathology of pregnant women with or without SARS-CoV-2 infection in the context of maternal PCR cycle threshold (CT) values. (2) This was a retrospective case-control study in a third-level health [...] Read more.
(1) This study aimed to evaluate characteristics, perinatal outcomes, and placental pathology of pregnant women with or without SARS-CoV-2 infection in the context of maternal PCR cycle threshold (CT) values. (2) This was a retrospective case-control study in a third-level health center in Mexico City with universal screening by RT-qPCR. The association of COVID-19 manifestations, preeclampsia, and preterm birth with maternal variables and CT values were assessed by logistic regression models and decision trees. (3) Accordingly, 828 and 298 women had a negative and positive test, respectively. Of those positive, only 2.6% of them presented mild to moderate symptoms. Clinical characteristics between both groups of women were similar. No associations between CT values were found for maternal features, such as pre-gestational BMI, age, and symptomatology. A significantly higher percentage of placental fibrinoid was seen with women with low CTs (<25; p < 0.01). Regarding perinatal outcomes, preeclampsia was found to be significantly associated with symptomatology but not with risk factors or CT values (p < 0.01, aOR = 14.72). Moreover, 88.9% of women diagnosed with COVID-19 at <35 gestational weeks and symptomatic developed preeclampsia. (4) The data support strong guidance for pregnancies with SARS-CoV-2 infection, in particular preeclampsia and placental pathology, which need further investigation. Full article
(This article belongs to the Collection SARS-CoV-2 and COVID-19)
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Review
Synergistic Impairment of the Neurovascular Unit by HIV-1 Infection and Methamphetamine Use: Implications for HIV-1-Associated Neurocognitive Disorders
Viruses 2021, 13(9), 1883; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091883 - 21 Sep 2021
Viewed by 619
Abstract
The neurovascular units (NVU) are the minimal functional units of the blood–brain barrier (BBB), composed of endothelial cells, pericytes, astrocytes, microglia, neurons, and the basement membrane. The BBB serves as an important interface for immune communication between the brain and peripheral circulation. Disruption [...] Read more.
The neurovascular units (NVU) are the minimal functional units of the blood–brain barrier (BBB), composed of endothelial cells, pericytes, astrocytes, microglia, neurons, and the basement membrane. The BBB serves as an important interface for immune communication between the brain and peripheral circulation. Disruption of the NVU by the human immunodeficiency virus-1 (HIV-1) induces dysfunction of the BBB and triggers inflammatory responses, which can lead to the development of neurocognitive impairments collectively known as HIV-1-associated neurocognitive disorders (HAND). Methamphetamine (METH) use disorder is a frequent comorbidity among individuals infected with HIV-1. METH use may be associated not only with rapid HIV-1 disease progression but also with accelerated onset and increased severity of HAND. However, the molecular mechanisms of METH-induced neuronal injury and cognitive impairment in the context of HIV-1 infection are poorly understood. In this review, we summarize recent progress in the signaling pathways mediating synergistic impairment of the BBB and neuronal injury induced by METH and HIV-1, potentially accelerating the onset or severity of HAND in HIV-1-positive METH abusers. We also discuss potential therapies to limit neuroinflammation and NVU damage in HIV-1-infected METH abusers. Full article
(This article belongs to the Special Issue HIV and Drugs of Abuse)
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Review
Mutation Rates, Mutation Frequencies, and Proofreading-Repair Activities in RNA Virus Genetics
Viruses 2021, 13(9), 1882; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091882 - 21 Sep 2021
Cited by 1 | Viewed by 675
Abstract
The error rate displayed during template copying to produce viral RNA progeny is a biologically relevant parameter of the replication complexes of viruses. It has consequences for virus–host interactions, and it represents the first step in the diversification of viruses in nature. Measurements [...] Read more.
The error rate displayed during template copying to produce viral RNA progeny is a biologically relevant parameter of the replication complexes of viruses. It has consequences for virus–host interactions, and it represents the first step in the diversification of viruses in nature. Measurements during infections and with purified viral polymerases indicate that mutation rates for RNA viruses are in the range of 10−3 to 10−6 copying errors per nucleotide incorporated into the nascent RNA product. Although viruses are thought to exploit high error rates for adaptation to changing environments, some of them possess misincorporation correcting activities. One of them is a proofreading-repair 3′ to 5′ exonuclease present in coronaviruses that may decrease the error rate during replication. Here we review experimental evidence and models of information maintenance that explain why elevated mutation rates have been preserved during the evolution of RNA (and some DNA) viruses. The models also offer an interpretation of why error correction mechanisms have evolved to maintain the stability of genetic information carried out by large viral RNA genomes such as the coronaviruses. Full article
(This article belongs to the Special Issue Viral Replication Complexes)
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Review
How Viruses Use the VCP/p97 ATPase Molecular Machine
Viruses 2021, 13(9), 1881; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091881 - 21 Sep 2021
Viewed by 589
Abstract
Viruses are obligate intracellular parasites that are dependent on host factors for their replication. One such host protein, p97 or the valosin-containing protein (VCP), is a highly conserved AAA ATPase that facilitates replication of diverse RNA- and DNA-containing viruses. The wide range of [...] Read more.
Viruses are obligate intracellular parasites that are dependent on host factors for their replication. One such host protein, p97 or the valosin-containing protein (VCP), is a highly conserved AAA ATPase that facilitates replication of diverse RNA- and DNA-containing viruses. The wide range of cellular functions attributed to this ATPase is consistent with its participation in multiple steps of the virus life cycle from entry and uncoating to viral egress. Studies of VCP/p97 interactions with viruses will provide important information about host processes and cell biology, but also viral strategies that take advantage of these host functions. The critical role of p97 in viral replication might be exploited as a target for development of pan-antiviral drugs that exceed the capability of virus-specific vaccines or therapeutics. Full article
(This article belongs to the Special Issue Chaperones and Viral-Host Interactions)
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Review
Myocardial Damage by SARS-CoV-2: Emerging Mechanisms and Therapies
Viruses 2021, 13(9), 1880; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091880 - 21 Sep 2021
Viewed by 728
Abstract
Evidence is emerging that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect various organs of the body, including cardiomyocytes and cardiac endothelial cells in the heart. This review focuses on the effects of SARS-CoV-2 in the heart after direct infection that can [...] Read more.
Evidence is emerging that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect various organs of the body, including cardiomyocytes and cardiac endothelial cells in the heart. This review focuses on the effects of SARS-CoV-2 in the heart after direct infection that can lead to myocarditis and an outline of potential treatment options. The main points are: (1) Viral entry: SARS-CoV-2 uses specific receptors and proteases for docking and priming in cardiac cells. Thus, different receptors or protease inhibitors might be effective in SARS-CoV-2-infected cardiac cells. (2) Viral replication: SARS-CoV-2 uses RNA-dependent RNA polymerase for replication. Drugs acting against ssRNA(+) viral replication for cardiac cells can be effective. (3) Autophagy and double-membrane vesicles: SARS-CoV-2 manipulates autophagy to inhibit viral clearance and promote SARS-CoV-2 replication by creating double-membrane vesicles as replication sites. (4) Immune response: Host immune response is manipulated to evade host cell attacks against SARS-CoV-2 and increased inflammation by dysregulating immune cells. Efficiency of immunosuppressive therapy must be elucidated. (5) Programmed cell death: SARS-CoV-2 inhibits programmed cell death in early stages and induces apoptosis, necroptosis, and pyroptosis in later stages. (6) Energy metabolism: SARS-CoV-2 infection leads to disturbed energy metabolism that in turn leads to a decrease in ATP production and ROS production. (7) Viroporins: SARS-CoV-2 creates viroporins that lead to an imbalance of ion homeostasis. This causes apoptosis, altered action potential, and arrhythmia. Full article
(This article belongs to the Special Issue COVID-19-Associated Myocarditis and Cardiac Pathology)
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Review
The Immunology of SARS-CoV-2 Infection and Vaccines in Solid Organ Transplant Recipients
Viruses 2021, 13(9), 1879; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091879 - 20 Sep 2021
Viewed by 699
Abstract
Since its outbreak in December 2019, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to an enormous rise in scientific response with an excess of COVID-19-related studies on the pathogenesis and potential therapeutic approaches. Solid [...] Read more.
Since its outbreak in December 2019, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to an enormous rise in scientific response with an excess of COVID-19-related studies on the pathogenesis and potential therapeutic approaches. Solid organ transplant (SOT) recipients are a heterogeneous population with long-lasting immunosuppression as a joining element. Immunocompromised patients are a vulnerable population with a high risk of severe infections and an increased infection-related mortality rate. It was postulated that the hyperinflammatory state due to cytokine release syndrome during severe COVID-19 could be alleviated by immunosuppressive therapy in SOT patients. On the other hand, it was previously established that T cell-mediated immunity, which is significantly weakened in SOT recipients, is the main component of antiviral immune responses. In this paper, we present the current state of science on COVID-19 immunology in relation to solid organ transplantation with prospective therapeutic and vaccination strategies in this population. Full article
(This article belongs to the Special Issue Pre-existing Immunity Effects on Viral Infections and Vaccinations)
Article
Neonatal Development in Prenatally Zika Virus-Exposed Infant Macaques with Dengue Immunity
Viruses 2021, 13(9), 1878; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091878 - 20 Sep 2021
Viewed by 494
Abstract
Infants exposed to Zika virus (ZIKV) prenatally may develop birth defects, developmental deficits, or remain asymptomatic. It is unclear why some infants are more affected than others, although enhancement of maternal ZIKV infection via immunity to an antigenically similar virus, dengue virus (DENV), [...] Read more.
Infants exposed to Zika virus (ZIKV) prenatally may develop birth defects, developmental deficits, or remain asymptomatic. It is unclear why some infants are more affected than others, although enhancement of maternal ZIKV infection via immunity to an antigenically similar virus, dengue virus (DENV), may play a role. We hypothesized that DENV immunity may worsen prenatal ZIKV infection and developmental deficits in offspring. We utilized a translational macaque model to examine how maternal DENV immunity influences ZIKV-exposed infant macaque neurodevelopment in the first month of life. We inoculated eight macaques with prior DENV infection with ZIKV, five macaques with ZIKV, and four macaques with saline. DENV/ZIKV-exposed infants had significantly worse visual orientation skills than ZIKV-exposed infants whose mothers were DENV-naive, with no differences in motor, sensory or state control development. ZIKV infection characteristics and pregnancy outcomes did not individually differ between dams with and without DENV immunity, but when multiple factors were combined in a multivariate model, maternal DENV immunity combined with ZIKV infection characteristics and pregnancy parameters predicted select developmental outcomes. We demonstrate that maternal DENV immunity exacerbates visual orientation and tracking deficits in ZIKV-exposed infant macaques, suggesting that human studies should evaluate how maternal DENV immunity impacts long-term neurodevelopment. Full article
(This article belongs to the Special Issue Pediatric Viral Infection Long-Term Consequences)
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Review
Vertical Transmission of SARS-CoV-2: A Systematic Review of Systematic Reviews
Viruses 2021, 13(9), 1877; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091877 - 20 Sep 2021
Viewed by 744
Abstract
The COVID-19 pandemic has hugely impacted global public health and economy. The COVID-19 has also shown potential impacts on maternal perinatal and neonatal outcomes. This systematic review aimed to summarize the evidence from existing systematic reviews about the effects of SARS-CoV-2 infections on [...] Read more.
The COVID-19 pandemic has hugely impacted global public health and economy. The COVID-19 has also shown potential impacts on maternal perinatal and neonatal outcomes. This systematic review aimed to summarize the evidence from existing systematic reviews about the effects of SARS-CoV-2 infections on maternal perinatal and neonatal outcomes. We searched PubMed, MEDLINE, Embase, and Web of Science in accordance with PRISMA guidelines, from 1 December 2019 to 7 July 2021, for published review studies that included case reports, primary studies, clinical practice guidelines, overviews, case-control studies, and observational studies. Systematic reviews that reported the plausibility of mother-to-child transmission of COVID-19 (also known as vertical transmission), maternal perinatal and neonatal outcomes, and review studies that addressed the effect of SARS-CoV-2 infection during pregnancy were also included. We identified 947 citations, of which 69 studies were included for further analysis. Most (>70%) of the mother-to-child infection was likely due to environmental exposure, although a significant proportion (about 20%) was attributable to potential vertical transmission of SARS-CoV-2. Further results of the review indicated that the mode of delivery of pregnant women infected with SARS-CoV-2 could not increase or decrease the risk of infection for the newborns (outcomes), thereby emphasizing the significance of breastfeeding. The issue of maternal perinatal and neonatal outcomes with SARS-CoV-2 infection continues to worsen during the ongoing COVID-19 pandemic, increasing maternal and neonatal mortality, stillbirth, ruptured ectopic pregnancies, and maternal depression. Based on this study, we observed increasing rates of cesarean delivery from mothers with SARS-CoV-2 infection. We also found that SARS-CoV-2 could be potentially transmitted vertically during the gestation period. However, more data are needed to further investigate and follow-up, especially with reports of newborns infected with SARS-CoV-2, in order to examine a possible long-term adverse effect. Full article
(This article belongs to the Special Issue COVID-19—Advances in Clinical and Epidemiological Aspects)
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Review
Lymphopenia Caused by Virus Infections and the Mechanisms Beyond
Viruses 2021, 13(9), 1876; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091876 - 20 Sep 2021
Viewed by 476
Abstract
Viral infections can give rise to a systemic decrease in the total number of lymphocytes in the blood, referred to as lymphopenia. Lymphopenia may affect the host adaptive immune responses and impact the clinical course of acute viral infections. Detailed knowledge on how [...] Read more.
Viral infections can give rise to a systemic decrease in the total number of lymphocytes in the blood, referred to as lymphopenia. Lymphopenia may affect the host adaptive immune responses and impact the clinical course of acute viral infections. Detailed knowledge on how viruses induce lymphopenia would provide valuable information into the pathogenesis of viral infections and potential therapeutic targeting. In this review, the current progress of viruses-induced lymphopenia is summarized and the potential mechanisms and factors involved are discussed. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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Article
A Reverse Transcription Recombinase-Aided Amplification Method for Rapid and Point-of-Care Detection of SARS-CoV-2, including Variants
Viruses 2021, 13(9), 1875; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091875 - 19 Sep 2021
Viewed by 587
Abstract
The worldwide pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its emergence of variants needs rapid and point-of-care testing methods for a broad diagnosis. The regular RT-qPCR is time-consuming and limited in central laboratories, so a broad and large-scale screening [...] Read more.
The worldwide pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its emergence of variants needs rapid and point-of-care testing methods for a broad diagnosis. The regular RT-qPCR is time-consuming and limited in central laboratories, so a broad and large-scale screening requirement calls for rapid and in situ methods. In this regard, a reverse transcription recombinase-aided amplification (RT-RAA) is proposed here for the rapid and point-of-care detection of SARS-CoV-2. A set of highly conserved primers and probes targeting more than 98% of SARS-CoV-2 strains, including currently circulating variants (four variants of concerns (VOCs) and three variants of interest (VOIs)), was used in this study. With the preferred primers, the RT-RAA assay showed a 100% specificity to SARS-CoV-2 from eight other respiratory RNA viruses. Moreover, the assay here is of a high sensitivity and 0.48 copies/μL can be detected within 25 min at a constant temperature (42 °C), which can be realized on portable equipment. Furthermore, the RT-RAA assay demonstrated its high agreement for the detection of SARS-CoV-2 in clinical specimens compared with RT-qPCR. The rapid, simple and point-of-care RT-RAA method is expected to be an appealing detection tool to detect SARS-CoV-2, including variants, in clinical diagnostic applications. Full article
(This article belongs to the Special Issue Viral Markers and the Diagnosis of COVID-19)
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Commentary
Chemistry and Bioinformatics Considerations in Using Next-Generation Sequencing Technologies to Inferring HIV Proviral DNA Genome-Intactness
Viruses 2021, 13(9), 1874; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091874 - 19 Sep 2021
Viewed by 594
Abstract
HIV persists via integration of the viral DNA into the human genome. The HIV DNA pool within an infected individual is a complex population that comprises both intact and defective viral genomes, each with a distinct integration site, in addition to a unique [...] Read more.
HIV persists via integration of the viral DNA into the human genome. The HIV DNA pool within an infected individual is a complex population that comprises both intact and defective viral genomes, each with a distinct integration site, in addition to a unique repertoire of viral quasi-species. Obtaining an accurate profile of the viral DNA pool is critical to understanding viral persistence and resolving interhost differences. Recent advances in next-generation deep sequencing (NGS) technologies have enabled the development of two sequencing assays to capture viral near-full- genome sequences at single molecule resolution (FLIP-seq) or to co-capture full-length viral genome sequences in conjunction with its associated viral integration site (MIP-seq). This commentary aims to provide an overview on both FLIP-seq and MIP-seq, discuss their strengths and limitations, and outline specific chemistry and bioinformatics concerns when using these assays to study HIV persistence. Full article
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Article
West Nile Virus and Tick-Borne Encephalitis Virus Are Endemic in Equids in Eastern Austria
Viruses 2021, 13(9), 1873; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091873 - 19 Sep 2021
Viewed by 780
Abstract
The emergence of West Nile virus (WNV) and Usutu virus (USUV) in addition to the autochthonous tick-borne encephalitis virus (TBEV) in Europe causes rising concern for public and animal health. The first equine case of West Nile neuroinvasive disease in Austria was diagnosed [...] Read more.
The emergence of West Nile virus (WNV) and Usutu virus (USUV) in addition to the autochthonous tick-borne encephalitis virus (TBEV) in Europe causes rising concern for public and animal health. The first equine case of West Nile neuroinvasive disease in Austria was diagnosed in 2016. As a consequence, a cross-sectional seroprevalence study was conducted in 2017, including 348 equids from eastern Austria. Serum samples reactive by ELISA for either flavivirus immunoglobulin G or M were further analyzed with the plaque reduction neutralization test (PRNT-80) to identify the specific etiologic agent. Neutralizing antibody prevalences excluding vaccinated equids were found to be 5.3% for WNV, 15.5% for TBEV, 0% for USUV, and 1.2% for WNV from autochthonous origin. Additionally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect WNV nucleic acid in horse sera and was found to be negative in all cases. Risk factor analysis did not identify any factors significantly associated with seropositivity. Full article
(This article belongs to the Special Issue Equine Viruses in Continental Europe)
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Article
Whole Genome Analysis of Human Rotaviruses Reveals Single Gene Reassortant Rotavirus Strains in Zambia
Viruses 2021, 13(9), 1872; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091872 - 18 Sep 2021
Viewed by 492
Abstract
Rotarix® vaccine was implemented nationwide in Zambia in 2013. In this study, four unusual strains collected in the post-vaccine period were subjected to whole genome sequencing and analysis. The four strains possessed atypical genotype constellations, with at least one reassortant genome segment [...] Read more.
Rotarix® vaccine was implemented nationwide in Zambia in 2013. In this study, four unusual strains collected in the post-vaccine period were subjected to whole genome sequencing and analysis. The four strains possessed atypical genotype constellations, with at least one reassortant genome segment within the constellation. One of the strains (UFS-NGS-MRC-DPRU4749) was genetically and phylogenetically distinct in the VP4 and VP1 gene segments. Pairwise analyses demonstrated several amino acid disparities in the VP4 antigenic sites of this strain compared to that of Rotarix®. Although the impact of these amino acid disparities remains to be determined, this study adds to our understanding of the whole genomes of reassortant strains circulating in Zambia following Rotarix® vaccine introduction. Full article
(This article belongs to the Special Issue Gastroenteritis Viruses 2021)
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Review
Towards a Systems Immunology Approach to Understanding Correlates of Protective Immunity against HCV
Viruses 2021, 13(9), 1871; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091871 - 18 Sep 2021
Viewed by 466
Abstract
Over the past decade, tremendous progress has been made in systems biology-based approaches to studying immunity to viral infections and responses to vaccines. These approaches that integrate multiple facets of the immune response, including transcriptomics, serology and immune functions, are now being applied [...] Read more.
Over the past decade, tremendous progress has been made in systems biology-based approaches to studying immunity to viral infections and responses to vaccines. These approaches that integrate multiple facets of the immune response, including transcriptomics, serology and immune functions, are now being applied to understand correlates of protective immunity against hepatitis C virus (HCV) infection and to inform vaccine development. This review focuses on recent progress in understanding immunity to HCV using systems biology, specifically transcriptomic and epigenetic studies. It also examines proposed strategies moving forward towards an integrated systems immunology approach for predicting and evaluating the efficacy of the next generation of HCV vaccines. Full article
(This article belongs to the Special Issue Novel Advances in Vaccines against HCV)
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Article
Multiple Occurrences of a 168-Nucleotide Deletion in SARS-CoV-2 ORF8, Unnoticed by Standard Amplicon Sequencing and Variant Calling Pipelines
Viruses 2021, 13(9), 1870; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091870 - 18 Sep 2021
Viewed by 812
Abstract
Genomic surveillance of the SARS-CoV-2 pandemic is crucial and mainly achieved by amplicon sequencing protocols. Overlapping tiled-amplicons are generated to establish contiguous SARS-CoV-2 genome sequences, which enable the precise resolution of infection chains and outbreaks. We investigated a SARS-CoV-2 outbreak in a local [...] Read more.
Genomic surveillance of the SARS-CoV-2 pandemic is crucial and mainly achieved by amplicon sequencing protocols. Overlapping tiled-amplicons are generated to establish contiguous SARS-CoV-2 genome sequences, which enable the precise resolution of infection chains and outbreaks. We investigated a SARS-CoV-2 outbreak in a local hospital and used nanopore sequencing with a modified ARTIC protocol employing 1200 bp long amplicons. We detected a long deletion of 168 nucleotides in the ORF8 gene in 76 samples from the hospital outbreak. This deletion is difficult to identify with the classical amplicon sequencing procedures since it removes two amplicon primer-binding sites. We analyzed public SARS-CoV-2 sequences and sequencing read data from ENA and identified the same deletion in over 100 genomes belonging to different lineages of SARS-CoV-2, pointing to a mutation hotspot or to positive selection. In almost all cases, the deletion was not represented in the virus genome sequence after consensus building. Additionally, further database searches point to other deletions in the ORF8 coding region that have never been reported by the standard data analysis pipelines. These findings and the fact that ORF8 is especially prone to deletions, make a clear case for the urgent necessity of public availability of the raw data for this and other large deletions that might change the physiology of the virus towards endemism. Full article
(This article belongs to the Collection Coronaviruses)
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Review
High Prevalence of Recombinant Porcine Endogenous Retroviruses (PERV-A/Cs) in Minipigs: A Review on Origin and Presence
Viruses 2021, 13(9), 1869; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091869 - 18 Sep 2021
Viewed by 336
Abstract
Minipigs play an important role in biomedical research and they have also been used as donor animals for preclinical xenotransplantations. Since zoonotic microorganisms including viruses can be transmitted when pig cells, tissues or organs are transplanted, virus safety is an important feature in [...] Read more.
Minipigs play an important role in biomedical research and they have also been used as donor animals for preclinical xenotransplantations. Since zoonotic microorganisms including viruses can be transmitted when pig cells, tissues or organs are transplanted, virus safety is an important feature in xenotransplantation. Whereas most porcine viruses can be eliminated from pig herds by different strategies, this is not possible for porcine endogenous retroviruses (PERVs). PERVs are integrated in the genome of pigs and some of them release infectious particles able to infect human cells. Whereas PERV-A and PERV-B are present in all pigs and can infect cells from humans and other species, PERV-C is present in most, but not all pigs and infects only pig cells. Recombinant viruses between PERV-A and PERV-C have been found in some pigs; these recombinants infect human cells and are characterized by high replication rates. PERV-A/C recombinants have been found mainly in minipigs of different origin. The possible reasons of this high prevalence of PERV-A/C in minipigs, including inbreeding and higher numbers and expression of replication-competent PERV-C in these animals, are discussed in this review. Based on these data, it is highly recommended to use only pig donors in clinical xenotransplantation that are negative for PERV-C. Full article
(This article belongs to the Section Animal Viruses)
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Article
Cytokine Response to SARS-CoV-2 Infection in Children
Viruses 2021, 13(9), 1868; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091868 - 18 Sep 2021
Viewed by 444
Abstract
The causal connection between serum biomarkers and COVID-19 severity or pathogenicity in children is unclear. The aim of this study was to describe clinical and immunological features of children affected by COVID-19. The secondary aim was to evaluate whether these cytokines could predict [...] Read more.
The causal connection between serum biomarkers and COVID-19 severity or pathogenicity in children is unclear. The aim of this study was to describe clinical and immunological features of children affected by COVID-19. The secondary aim was to evaluate whether these cytokines could predict severity of COVID-19. All children (aged 0−18) admitted to the Pediatric Emergency Department and tested with nasopharyngeal swab for SARS-CoV-2 were recruited and assigned to three groups: COVID-19, other infections, control group. Clinical and laboratory data of these patients, including circulating cytokine levels, were analyzed in three groups. Fever was the most frequent symptom in COVID-19 (67.3%). Neutropenia was found in the COVID-19 group (p < 0.05); no difference was observed for lymphocyte counts in the three groups. Higher levels of IL-6 and TNF-alpha were found in the COVID-19 group compared to other infections and control groups (p = 0.014 and p = 0.001, respectively). Whereas, in the COVID-19 group, no difference was observed as for the same cytokines among sub-groups of different disease severity (p = 0.7 and p = 0.8). Serum levels of IL-6 and TNF-alpha were higher in COVID-19 children than in children with other infectious diseases, but those levels did not correlate with disease severity. Clinical studies in a large pediatric population are necessary to better define the role of the immune-mediated response in SARS-CoV-2 infections in children. Full article
(This article belongs to the Topic Burden of COVID-19 in Different Countries)
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Article
Direct Metatranscriptomic Survey of the Sunflower Microbiome and Virome
Viruses 2021, 13(9), 1867; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091867 - 18 Sep 2021
Viewed by 453
Abstract
Sunflowers (Helianthus annuus L.) are susceptible to multiple diseases in field production. In this study, we collected diseased sunflower leaves in fields located in South Dakota, USA, for virome investigation. The leaves showed visible symptoms on the foliage, indicating phomopsis and rust [...] Read more.
Sunflowers (Helianthus annuus L.) are susceptible to multiple diseases in field production. In this study, we collected diseased sunflower leaves in fields located in South Dakota, USA, for virome investigation. The leaves showed visible symptoms on the foliage, indicating phomopsis and rust infections. To identify the viruses potentially associated with the disease diagnosed, symptomatic leaves were obtained from diseased plants. Total RNA was extracted corresponding to each disease diagnosed to generate libraries for paired-end high throughput sequencing. Short sequencing reads were assembled de novo and the contigs with similarities to viruses were identified by aligning against a custom protein database. We report the discovery of two novel mitoviruses, four novel partitiviruses, one novel victorivirus, and nine novel totiviruses based on similarities to RNA-dependent RNA polymerases and capsid proteins. Contigs similar to bean yellow mosaic virus and Sclerotinia sclerotiorum hypovirulence-associated DNA virus were also detected. To the best of our knowledge, this is the first report of direct metatranscriptomics discovery of viruses associated with fungal infections of sunflowers bypassing culturing. These newly discovered viruses represent a natural genetic resource from which we can further develop potential biopesticide to control sunflower diseases. Full article
(This article belongs to the Collection Mycoviruses)
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Article
Construction of a Recombinant Porcine Epidemic Diarrhea Virus Encoding Nanoluciferase for High-Throughput Screening of Natural Antiviral Products
Viruses 2021, 13(9), 1866; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091866 - 18 Sep 2021
Viewed by 465
Abstract
Porcine epidemic diarrhea virus (PEDV) is the predominant cause of an acute, highly contagious enteric disease in neonatal piglets. There are currently no approved drugs against PEDV infection. Here, we report the development of a nanoluciferase (NLuc)-based high-throughput screening (HTS) platform to identify [...] Read more.
Porcine epidemic diarrhea virus (PEDV) is the predominant cause of an acute, highly contagious enteric disease in neonatal piglets. There are currently no approved drugs against PEDV infection. Here, we report the development of a nanoluciferase (NLuc)-based high-throughput screening (HTS) platform to identify novel anti-PEDV compounds. We constructed a full-length cDNA clone for a cell-adapted PEDV strain YN150. Using reverse genetics, we replaced the open reading frame 3 (ORF3) in the viral genome with an NLuc gene to engineer a recombinant PEDV expressing NLuc (rPEDV-NLuc). rPEDV-NLuc produced similar plaque morphology and showed similar growth kinetics compared with the wild-type PEDV in vitro. Remarkably, the level of luciferase activity could be stably detected in rPEDV-NLuc-infected cells and exhibited a strong positive correlation with the viral titers. Given that NLuc expression represents a direct readout of PEDV replication, anti-PEDV compounds could be easily identified by quantifying the NLuc activity. Using this platform, we screened for the anti-PEDV compounds from a library of 803 natural products and identified 25 compounds that could significantly inhibit PEDV replication. Interestingly, 7 of the 25 identified compounds were natural antioxidants, including Betulonic acid, Ursonic acid, esculetin, lithocholic acid, nordihydroguaiaretic acid, caffeic acid phenethyl ester, and grape seed extract. As expected, all of the antioxidants could potently reduce PEDV-induced oxygen species production, which, in turn, inhibit PEDV replication in a dose-dependent manner. Collectively, our findings provide a powerful platform for the rapid screening of promising therapeutic compounds against PEDV infection. Full article
(This article belongs to the Topic Veterinary Infectious Diseases)
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Review
Viruses Infecting the European Catfish (Silurus glanis)
Viruses 2021, 13(9), 1865; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091865 - 18 Sep 2021
Viewed by 348
Abstract
In aquaculture, disease management and pathogen control are key for a successful fish farming industry. In past years, European catfish farming has been flourishing. However, devastating fish pathogens including limiting fish viruses are considered a big threat to further expanding of the industry. [...] Read more.
In aquaculture, disease management and pathogen control are key for a successful fish farming industry. In past years, European catfish farming has been flourishing. However, devastating fish pathogens including limiting fish viruses are considered a big threat to further expanding of the industry. Even though mainly the ranavirus (Iridoviridea) and circovirus (Circoviridea) infections are considered well- described in European catfish, more other agents including herpes-, rhabdo or papillomaviruses are also observed in the tissues of catfish with or without any symptoms. The etiological role of these viruses has been unclear until now. Hence, there is a requisite for more detailed information about the latter and the development of preventive and therapeutic approaches to complete them. In this review, we summarize recent knowledge about viruses that affect the European catfish and describe their origin, distribution, molecular characterisation, and phylogenetic classification. We also highlight the knowledge gaps, which need more in-depth investigations in the future. Full article
(This article belongs to the Section Animal Viruses)
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Article
Patterns of Coevolutionary Adaptations across Time and Space in Mouse Gammaretroviruses and Three Restrictive Host Factors
Viruses 2021, 13(9), 1864; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091864 - 18 Sep 2021
Viewed by 333
Abstract
The classical laboratory mouse strains are genetic mosaics of three Mus musculus subspecies that occupy distinct regions of Eurasia. These strains and subspecies carry infectious and endogenous mouse leukemia viruses (MLVs) that can be pathogenic and mutagenic. MLVs evolved in concert with restrictive [...] Read more.
The classical laboratory mouse strains are genetic mosaics of three Mus musculus subspecies that occupy distinct regions of Eurasia. These strains and subspecies carry infectious and endogenous mouse leukemia viruses (MLVs) that can be pathogenic and mutagenic. MLVs evolved in concert with restrictive host factors with some under positive selection, including the XPR1 receptor for xenotropic/polytropic MLVs (X/P-MLVs) and the post-entry restriction factor Fv1. Since positive selection marks host-pathogen genetic conflicts, we examined MLVs for counter-adaptations at sites that interact with XPR1, Fv1, and the CAT1 receptor for ecotropic MLVs (E-MLVs). Results describe different co-adaptive evolutionary paths within the ranges occupied by these virus-infected subspecies. The interface of CAT1, and the otherwise variable E-MLV envelopes, is highly conserved; antiviral protection is afforded by the Fv4 restriction factor. XPR1 and X/P-MLVs variants show coordinate geographic distributions, with receptor critical sites in envelope, under positive selection but with little variation in envelope and XPR1 in mice carrying P-ERVs. The major Fv1 target in the viral capsid is under positive selection, and the distribution of Fv1 alleles is subspecies-correlated. These data document adaptive, spatial and temporal, co-evolutionary trajectories at the critical interfaces of MLVs and the host factors that restrict their replication. Full article
(This article belongs to the Special Issue RNA Viruses: Structure, Adaptation, and Evolution)
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Article
Bromodeoxyuridine Labelling to Determine Viral DNA Localization in Fluorescence and Electron Microscopy: The Case of Adenovirus
Viruses 2021, 13(9), 1863; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091863 - 18 Sep 2021
Cited by 1 | Viewed by 364
Abstract
The localization of viral nucleic acids in the cell is essential for understanding the infectious cycle. One of the strategies developed for this purpose is the use of nucleotide analogs such as bromodeoxyuridine (BrdU, analog to thymine) or bromouridine (BrU, analog of uridine), [...] Read more.
The localization of viral nucleic acids in the cell is essential for understanding the infectious cycle. One of the strategies developed for this purpose is the use of nucleotide analogs such as bromodeoxyuridine (BrdU, analog to thymine) or bromouridine (BrU, analog of uridine), which are incorporated into the nucleic acids during replication or transcription. In adenovirus infections, BrdU has been used to localize newly synthesized viral genomes in the nucleus, where it is key to distinguish between host and viral DNA. Here, we describe our experience with methodological variations of BrdU labeling to localize adenovirus genomes in fluorescence and electron microscopy. We illustrate the need to define conditions in which most of the newly synthesized DNA corresponds to the virus and not the host, and the amount of BrdU provided is enough to incorporate to the new DNA molecules without hampering the cell metabolism. We hope that our discussion of problems encountered and solutions implemented will help other researches interested in viral genome localization in infected cells. Full article
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Obituary
Tribute to Professor Stefan Kunz
Viruses 2021, 13(9), 1862; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091862 - 18 Sep 2021
Viewed by 630
Abstract
It has been a year since Stefan Kunz, a Full Professor since 2017 at the Faculty of Biology and Medicine of the University of Lausanne, Switzerland, passed away [...] Full article
(This article belongs to the Special Issue In Memory of Stefan Kunz)
Brief Report
Human Papillomavirus-Related Multiphenotypic Sinonasal Carcinoma—An Even Broader Tumor Entity?
Viruses 2021, 13(9), 1861; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091861 - 17 Sep 2021
Viewed by 384
Abstract
Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a recently defined tumor subtype with apparent favorable clinical outcome despite aggressive histomorphology. However, in recent years, additional numbers of cases, with more variable features and at locations outside the sinonasal region, have complicated the [...] Read more.
Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a recently defined tumor subtype with apparent favorable clinical outcome despite aggressive histomorphology. However, in recent years, additional numbers of cases, with more variable features and at locations outside the sinonasal region, have complicated the definition of HMSC. Here, we have performed a systematic review of all cases described so far in order to accumulate more knowledge. We identified 127 articles published between 2013 and 2021, of which 21 presented unique cases. In total, 79 unique patient cases were identified and their clinical and micromorphological nature are herein summarized. In our opinion, better clinical follow-up data and a more detailed tumor characterization are preferably needed before HMSC can finally be justified as its own tumor entity. Full article
(This article belongs to the Special Issue HPV in the Head and Neck Region)
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Review
Challenges in the Application of Glyco-Technology to Hepatitis B Virus Therapy and Diagnosis
Viruses 2021, 13(9), 1860; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091860 - 17 Sep 2021
Viewed by 491
Abstract
Hepatitis B virus (HBV) is a major pathogen that causes acute/chronic hepatitis. Continuous HBV infection can lead to the development of hepatocellular carcinoma (HCC). Although several different anti-HBV treatments are available for chronic hepatitis B patients, discontinuing these medications is difficult. Patients with [...] Read more.
Hepatitis B virus (HBV) is a major pathogen that causes acute/chronic hepatitis. Continuous HBV infection can lead to the development of hepatocellular carcinoma (HCC). Although several different anti-HBV treatments are available for chronic hepatitis B patients, discontinuing these medications is difficult. Patients with chronic hepatitis B at high risk for HCC therefore require close observation. However, no suitable biomarkers for detecting high-risk groups for HCC exist, except for serum HBV-DNA, but a number of HCC biomarkers are used clinically, such as alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-II). Glycosylation is an important post-translational protein modification involved in many human pathologic conditions. HBV surface proteins contain various oligosaccharides, and several reports have described their biological functions. Inhibition of HBV glycosylation represents a potential novel anti-HBV therapy. It is thought that glycosylation of hepatocytes/hepatoma cells is also important for HBV infection, as it prevents HBV from infecting cells other than hepatocytes, even if the cells express the HBV receptor. In this review, we summarize considerable research regarding the relationship between HBV and glycosylation as it relates to the development of novel diagnostic tests and therapies for HBV. Full article
(This article belongs to the Special Issue Hepatitis B Virus: Its Life Cycle and the Therapeutic Targets)
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Article
Comparative Analysis of Novel Strains of Porcine Astrovirus Type 3 in the USA
Viruses 2021, 13(9), 1859; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091859 - 17 Sep 2021
Viewed by 424
Abstract
Porcine astrovirus type 3 (PoAstV3) has been previously identified as a cause of polioencephalomyelitis in swine and continues to cause disease in the US swine industry. Herein, we describe the characterization of both untranslated regions, frameshifting signal, putative genome-linked virus protein (VPg) and [...] Read more.
Porcine astrovirus type 3 (PoAstV3) has been previously identified as a cause of polioencephalomyelitis in swine and continues to cause disease in the US swine industry. Herein, we describe the characterization of both untranslated regions, frameshifting signal, putative genome-linked virus protein (VPg) and conserved antigenic epitopes of several novel PoAstV3 genomes. Twenty complete coding sequences (CDS) were obtained from 32 diagnostic cases originating from 11 individual farms/systems sharing a nucleotide (amino acid) percent identity of 89.74–100% (94.79–100%), 91.9–100% (96.3–100%) and 90.71–100% (93.51–100%) for ORF1a, ORF1ab and ORF2, respectively. Our results indicate that the 5′UTR of PoAstV3 is highly conserved highlighting the importance of this region in translation initiation while their 3′UTR is moderately conserved among strains, presenting alternative configurations including multiple putative protein binding sites and pseudoknots. Moreover, two predicted conserved antigenic epitopes were identified matching the 3′ termini of VP27 of PoAstV3 USA strains. These epitopes may aid in the design and development of vaccine components and diagnostic assays useful to control outbreaks of PoAstV3-associated CNS disease. In conclusion, this is the first analysis predicting the structure of important regulatory motifs of neurotropic mamastroviruses, which differ from those previously described in human astroviruses. Full article
(This article belongs to the Topic Veterinary Infectious Diseases)
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Review
The Clonal Expansion Dynamics of the HIV-1 Reservoir: Mechanisms of Integration Site-Dependent Proliferation and HIV-1 Persistence
Viruses 2021, 13(9), 1858; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091858 - 17 Sep 2021
Viewed by 758
Abstract
More than 50% of the HIV-1 latent reservoir is maintained by clonal expansion. The clonally expanded HIV-1-infected cells can contribute to persistent nonsuppressible low-level viremia and viral rebound. HIV-1 integration site and proviral genome landscape profiling reveals the clonal expansion dynamics of HIV-1-infected [...] Read more.
More than 50% of the HIV-1 latent reservoir is maintained by clonal expansion. The clonally expanded HIV-1-infected cells can contribute to persistent nonsuppressible low-level viremia and viral rebound. HIV-1 integration site and proviral genome landscape profiling reveals the clonal expansion dynamics of HIV-1-infected cells. In individuals under long-term suppressive antiretroviral therapy (ART), HIV-1 integration sites are enriched in specific locations in certain cancer-related genes in the same orientation as the host transcription unit. Single-cell transcriptome analysis revealed that HIV-1 drives aberrant cancer-related gene expression through HIV-1-to-host RNA splicing. Furthermore, the HIV-1 promoter dominates over the host gene promoter and drives high levels of cancer-related gene expression. When HIV-1 integrates into cancer-related genes and causes gain of function of oncogenes or loss of function of tumor suppressor genes, HIV-1 insertional mutagenesis drives the proliferation of HIV-1-infected cells and may cause cancer in rare cases. HIV-1-driven aberrant cancer-related gene expression at the integration site can be suppressed by CRISPR-mediated inhibition of the HIV-1 promoter or by HIV-1 suppressing agents. Given that ART does not suppress HIV-1 promoter activity, therapeutic agents that suppress HIV-1 transcription and halt the clonal expansion of HIV-1-infected cells should be explored to block the clonal expansion of the HIV-1 latent reservoir. Full article
(This article belongs to the Special Issue HIV Infection and Spread between T Cells)
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