Editorial

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Open AccessEditorial

Editorial for the Special Issue: Molecular Epidemiology, Diagnostics and Management of Respiratory Virus Infections

by Hirokazu Kimura, Yuriko Hayashi, Mitsuru Sada, Haruyuki Ishii, Takeshi Tsugawa and Akihide Ryo

Microorganisms 2020, 8(12), 2041; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8122041 - 20 Dec 2020

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Abstract

In Japan, there is a proverb that the common cold is associated with all diseases [...] Full article

(This article belongs to the Special Issue Molecular Epidemiology, Diagnostics and Management of Respiratory Virus Infections)

Research

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20 pages, 3921 KiB

Open AccessArticle

Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model

by Qingyu Wu, Ilka Jorde, Olivia Kershaw, Andreas Jeron, Dunja Bruder, Jens Schreiber and Sabine Stegemann-Koniszewski

Microorganisms 2020, 8(12), 1878; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8121878 - 27 Nov 2020

Cited by 4 | Viewed by 2211

Abstract

Allergic airway inflammation (AAI) involves T helper cell type 2 (Th2) and pro-inflammatory responses to aeroallergens and many predisposing factors remain elusive. Influenza A virus (IAV) is a major human pathogen that causes acute respiratory infections and induces specific immune responses essential for [...] Read more.

Allergic airway inflammation (AAI) involves T helper cell type 2 (Th2) and pro-inflammatory responses to aeroallergens and many predisposing factors remain elusive. Influenza A virus (IAV) is a major human pathogen that causes acute respiratory infections and induces specific immune responses essential for viral clearance and resolution of the infection. Beyond acute infection, IAV has been shown to persistently affect lung homeostasis and respiratory immunity. Here we asked how resolved IAV infection affects subsequently induced AAI. Mice infected with a sublethal dose of IAV were sensitized and challenged in an ovalbumin mediated mouse model for AAI after resolution of the acute viral infection. Histological changes, respiratory leukocytes, cytokines and airway hyperreactivity were analyzed in resolved IAV infection alone and in AAI with and without previous IAV infection. More than five weeks after infection, we detected persistent pneumonia with increased activated CD4⁺ and CD8⁺ lymphocytes as well as dendritic cells and MHCII expressing macrophages in the lung. Resolved IAV infection significantly affected subsequently induced AAI on different levels including morphological changes, respiratory leukocytes and lymphocytes as well as the pro-inflammatory cytokine responses, which was clearly diminished. We conclude that IAV has exceptional persisting effects on respiratory immunity with substantial consequences for subsequently induced AAI. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Diagnostics and Management of Respiratory Virus Infections)

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9 pages, 2433 KiB

Open AccessArticle

Detection of Parechovirus A1 with Monoclonal Antibody against Capsid Protein VP0

by Ming-Hsiang Kung, Ming-Wei Jan, Jih-Jung Chen, Yi-Chien Shieh and Tsung-Hsien Chang

Microorganisms 2020, 8(11), 1794; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8111794 - 16 Nov 2020

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Abstract

Parechovirus A (PeV-A; human parechovirus) causes mild infections and severe diseases such as neonatal sepsis, encephalitis, and cardiomyopathy in young children. Among the 19 types of PeV-A, PeV-A1 is the most common type of infection. We have previously established an immunofluorescence assay for [...] Read more.

Parechovirus A (PeV-A; human parechovirus) causes mild infections and severe diseases such as neonatal sepsis, encephalitis, and cardiomyopathy in young children. Among the 19 types of PeV-A, PeV-A1 is the most common type of infection. We have previously established an immunofluorescence assay for detecting multiple PeV-A types with a polyclonal antibody against the conserved epitope of VP0. Although the polyclonal antibody is useful for PeV-A diagnosis, it could not distinguish the PeV-A genotypes. Thus, the development of a specific monoclonal antibody for identifying the common infection of PeV-A1 would be beneficial in clinical diagnosis practice. In this study, the recombinant full-length PeV-A1 VP0 protein was used in mouse immunization; a total 10 hybridomas were established. After evaluation by immunoblotting and fluorescence assays, six hybridoma clones with monoclonal antibody (mAb) production were confirmed. These mAbs, which specifically recognize viral protein PeV-A1 VP0 without cross-reactivity to PeV-A3, will prove useful in research and PeV-A1 diagnosis. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Diagnostics and Management of Respiratory Virus Infections)

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14 pages, 2201 KiB

Open AccessArticle

Phylogeography of 27,000 SARS-CoV-2 Genomes: Europe as the Major Source of the COVID-19 Pandemic

by Teresa Rito, Martin B. Richards, Maria Pala, Margarida Correia-Neves and Pedro A. Soares

Microorganisms 2020, 8(11), 1678; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8111678 - 29 Oct 2020

Cited by 15 | Viewed by 11482

Abstract

The novel coronavirus SARS-CoV-2 emerged from a zoonotic transmission in China towards the end of 2019, rapidly leading to a global pandemic on a scale not seen for a century. In order to cast fresh light on the spread of the virus and [...] Read more.

The novel coronavirus SARS-CoV-2 emerged from a zoonotic transmission in China towards the end of 2019, rapidly leading to a global pandemic on a scale not seen for a century. In order to cast fresh light on the spread of the virus and on the effectiveness of the containment measures adopted globally, we used 26,869 SARS-CoV-2 genomes to build a phylogeny with 20,247 mutation events and adopted a phylogeographic approach. We confirmed that the phylogeny pinpoints China as the origin of the pandemic with major founders worldwide, mainly during January 2020. However, a single specific East Asian founder underwent massive radiation in Europe and became the main actor of the subsequent spread worldwide during March 2020. This lineage accounts for the great majority of cases detected globally and even spread back to the source in East Asia. Despite an East Asian source, therefore, the global pandemic was mainly fueled by its expansion across and out of Europe. It seems likely that travel bans established throughout the world in the second half of March helped to decrease the number of intercontinental exchanges, particularly from mainland China, but were less effective between Europe and North America where exchanges in both directions are visible up to April, long after bans were imposed. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Diagnostics and Management of Respiratory Virus Infections)

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9 pages, 1236 KiB

Open AccessCommunication

Detailed Molecular Interactions of Favipiravir with SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza Virus Polymerases In Silico

by Mitsuru Sada, Takeshi Saraya, Haruyuki Ishii, Kaori Okayama, Yuriko Hayashi, Takeshi Tsugawa, Atsuyoshi Nishina, Koichi Murakami, Makoto Kuroda, Akihide Ryo and Hirokazu Kimura

Microorganisms 2020, 8(10), 1610; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8101610 - 20 Oct 2020

Cited by 30 | Viewed by 5011

Abstract

Favipiravir was initially developed as an antiviral drug against influenza and is currently used in clinical trials against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19). This agent is presumably involved in RNA chain termination during influenza virus replication, although the molecular interactions [...] Read more.

Favipiravir was initially developed as an antiviral drug against influenza and is currently used in clinical trials against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19). This agent is presumably involved in RNA chain termination during influenza virus replication, although the molecular interactions underlying its potential impact on the coronaviruses including SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) remain unclear. We performed in silico studies to elucidate detailed molecular interactions between favipiravir and the SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza virus RNA-dependent RNA polymerases (RdRp). As a result, no interactions between favipiravir ribofuranosyl-5′-triphosphate (F-RTP), the active form of favipiravir, and the active sites of RdRps (PB1 proteins) from influenza A (H1N1)pdm09 virus were found, yet the agent bound to the tunnel of the replication genome of PB1 protein leading to the inhibition of replicated RNA passage. In contrast, F-RTP bound to the active sites of coronavirus RdRp in the presence of the agent and RdRp. Further, the agent bound to the replicated RNA terminus in the presence of agent, magnesium ions, nucleotide triphosphate, and RdRp proteins. These results suggest that favipiravir exhibits distinct mechanisms of action against influenza virus and various coronaviruses. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Diagnostics and Management of Respiratory Virus Infections)

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12 pages, 2108 KiB

Open AccessArticle

Development of Monoclonal Antibodies and Antigen-Capture ELISA for Human Parechovirus Type 3

by Keiko Goto, Yutaro Yamaoka, Hajera Khatun, Kei Miyakawa, Mayuko Nishi, Noriko Nagata, Toshikazu Yanaoka, Hirokazu Kimura and Akihide Ryo

Microorganisms 2020, 8(9), 1437; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8091437 - 19 Sep 2020

Cited by 3 | Viewed by 3129

Abstract

Human parechovirus type 3 (HPeV3) is an etiologic agent of respiratory diseases, meningitis, and sepsis-like illness in both infants and adults. Monoclonal antibodies (mAbs) can be a promising diagnostic tool for antigenic diseases such as virus infection, as they offer a high specificity [...] Read more.

Human parechovirus type 3 (HPeV3) is an etiologic agent of respiratory diseases, meningitis, and sepsis-like illness in both infants and adults. Monoclonal antibodies (mAbs) can be a promising diagnostic tool for antigenic diseases such as virus infection, as they offer a high specificity toward a specific viral antigen. However, to date, there is no specific mAb available for the diagnosis of HPeV3 infection. In this study, we developed and characterized mAbs specific for HPeV3 capsid protein VP0. We used cell-free, wheat germ-synthesized viral VP0 protein for immunizing BALB/c mice to generate hybridomas. From the resultant hybridoma clones, we selected nine clones producing mAbs reactive to the HPeV3-VP0 antigen, based on enzyme-linked immunosorbent assay (ELISA). Epitope mapping showed that these mAbs recognized three distinct domains in HPeV3 VP0. Six mAbs recognized HPeV3 specifically and the other three mAbs showed cross-reactivity with other HPeVs. Using the HPeV3-specific mAbs, we then developed an ELISA for viral antigen detection that could be reliably used for laboratory diagnosis of HPeV3. This ELISA system exhibited no cross-reactivity with other related viruses. Our newly developed mAbs would, thus, provide a useful set of tools for future research and ensure HPeV3-specific diagnosis. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Diagnostics and Management of Respiratory Virus Infections)

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9 pages, 256 KiB

Open AccessArticle

Analytical Performances of the Panther Fusion System for the Detection of Respiratory Viruses in the French National Reference Centre of Lyon, France

by Maxime Pichon, Martine Valette, Isabelle Schuffenecker, Geneviève Billaud and Bruno Lina

Microorganisms 2020, 8(9), 1371; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8091371 - 07 Sep 2020

Cited by 2 | Viewed by 2066

Abstract

Respiratory infection are mainly caused by viral pathogens. During the 2017–2018 epidemic season, Panther Fusion^® Respiratory kits (Influenza virus A&B (FluA&B), respiratory syncytial virus (RSV), adenovirus (ADV), metapneumovirus (MPV), rhinovirus (RV), parainfluenzae virus (PIV), were compared to the Respiratory MultiWells System r-gene. [...] Read more.

Respiratory infection are mainly caused by viral pathogens. During the 2017–2018 epidemic season, Panther Fusion^® Respiratory kits (Influenza virus A&B (FluA&B), respiratory syncytial virus (RSV), adenovirus (ADV), metapneumovirus (MPV), rhinovirus (RV), parainfluenzae virus (PIV), were compared to the Respiratory MultiWells System r-gene. Respiratory clinical specimens were tested retrospectively (n = 268) and prospectively (n = 463). Analytical performances were determined (sensitivity –Sep-, specificity –Spe- and κ) considering concordances of ≥2 molecular testing specific to each viral target (discrepant results were verified at the National Reference Centres for Enteroviruses or Respiratory viruses, Lyon, France). After retrospective (and prospective) testing, Sep, Spe, and κ were 100% (97.7%), 100% (99%) and 100% (94%) for FluA: 100% (95.5%), 100% (99.3%) and 100% (94%) for FluB, and 100% (88.5%), 100% (98.7%) and 100% (89%) for RSV; 82.1% (41.7%), 100% (99.5%) and 86% (54%) for ADV; 94.7% (73.7%), 96.1% (98.0%) and 91% (65%) for MPV; 96.1% (94.6%), 90.2% (98.5%) and 86% (91%) for HRV; and 90% (72.7%), 100% (99.3%) and 91% (72%), respectively, for PIV. Analytical performances were above 85% for all viruses except for ADV, MPV and PIV, confirming the analytical performance of the Panther Fusion system, a high throughput system with reduced turn-around-time, when compared to non-automated systems. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Diagnostics and Management of Respiratory Virus Infections)

14 pages, 4491 KiB

Open AccessArticle

Recent Molecular Evolution of Human Metapneumovirus (HMPV): Subdivision of HMPV A2b Strains

by Naganori Nao, Miwako Saikusa, Ko Sato, Tsuyoshi Sekizuka, Shuzo Usuku, Nobuko Tanaka, Hidekazu Nishimura and Makoto Takeda

Microorganisms 2020, 8(9), 1280; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8091280 - 21 Aug 2020

Cited by 20 | Viewed by 3285

Abstract

Human metapneumovirus (HMPV) is a major etiological agent of acute respiratory infections in humans. HMPV has been circulating worldwide for more than six decades and is currently divided into five agreed-upon subtypes: A1, A2a, A2b, B1, and B2. Recently, the novel HMPV subtypes [...] Read more.

Human metapneumovirus (HMPV) is a major etiological agent of acute respiratory infections in humans. HMPV has been circulating worldwide for more than six decades and is currently divided into five agreed-upon subtypes: A1, A2a, A2b, B1, and B2. Recently, the novel HMPV subtypes A2c, A2b1, and A2b2 have been proposed. However, the phylogenetic and evolutionary relationships between these recently proposed HMPV subtypes are unclear. Here, we report a genome-wide phylogenetic and evolutionary analysis of 161 HMPV strains, including unique HMPV subtype A2b strains with a 180- or 111-nucleotide duplication in the G gene (nt-dup). Our data demonstrate that the HMPV A2b subtype contains two distinct subtypes, A2b1 and A2b2, and that the HMPV subtypes A2c and A2b2 may be different names for the same subtype. HMPV A2b strains with a nt-dup also belong to subtype A2b2. Molecular evolutionary analyses indicate that subtypes A2b1 and A2b2 diverged from subtype A2b around a decade after the subtype A2 was divided into the subtypes A2a and A2b. These data support the A2b1 and A2b2 subtypes proposed in 2012 and are essential for the unified classification of HMPV subtype A2 strains, which is important for future HMPV surveillance and epidemiological studies. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Diagnostics and Management of Respiratory Virus Infections)

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12 pages, 1343 KiB

Open AccessArticle

Increasing Cytomegalovirus Detection Rate from Respiratory Tract Specimens by a New Laboratory-Developed Automated Molecular Diagnostic Test

by Huey-Pin Tsai, Chun-Sheng Yeh, I-Ting Lin, Wen-Chien Ko and Jen-Ren Wang

Microorganisms 2020, 8(7), 1063; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8071063 - 16 Jul 2020

Cited by 3 | Viewed by 2590

Abstract

Lots of automated molecular methods for detecting cytomegalovirus (CMV) DNA in the blood are available, but seldom for various clinical specimens. This study was designed to establish a highly sensitive automated assay to detect CMV DNA in non-blood specimens. We designed a new [...] Read more.

Lots of automated molecular methods for detecting cytomegalovirus (CMV) DNA in the blood are available, but seldom for various clinical specimens. This study was designed to establish a highly sensitive automated assay to detect CMV DNA in non-blood specimens. We designed a new QMT assay using QIAGEN artus CMV RG polymerase chain reaction (Q-CMV PCR) kit applied on the BD MAX system and compared with the other assays, including an RGQ assay (LabTurbo auto-extraction combined Q-CMV PCR kit on Rotor-Gene-Q instrument), and in-house PCR assay. A total of 1067 various clinical samples, including 426 plasma, 293 respiratory tract specimens (RTS), 127 stool, 101 cerebral spinal fluid, 90 vitreous humours were analysed. Examining CMV DNA in simultaneous specimens of the same immunocompromised patient with respiratory symptoms, the detection rate of RTS (93.6%, 88/94) was significant higher than plasma (65.9%, 62/94). The positive rates for plasma samples with a low CMV viral load (<137 IU/mL) and diagnostic sensitivity of QMT, RGQ, and in-house assays were 65% and 99.1%, 45% and 100%, 5% and 65.5%, respectively. The QMT assay performs better, with shorter operational and turnaround time than the other assays, enabling the effective and early detection of CMV infection in various clinical specimens, particularly for RTS. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Diagnostics and Management of Respiratory Virus Infections)

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29 pages, 2079 KiB

Open AccessArticle

Systematic Review of the Respiratory Syncytial Virus (RSV) Prevalence, Genotype Distribution, and Seasonality in Children from the Middle East and North Africa (MENA) Region

by Hadi M. Yassine, Muhammad U. Sohail, Nadin Younes and Gheyath K. Nasrallah

Microorganisms 2020, 8(5), 713; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8050713 - 11 May 2020

Cited by 30 | Viewed by 5953

Abstract

Respiratory syncytial virus (RSV) is one of the most common viruses to infect children worldwide and is the leading cause of lower respiratory tract illness (LRI) in infants. This study aimed to conduct a systematic review by collecting and reviewing all the published [...] Read more.

Respiratory syncytial virus (RSV) is one of the most common viruses to infect children worldwide and is the leading cause of lower respiratory tract illness (LRI) in infants. This study aimed to conduct a systematic review by collecting and reviewing all the published knowledge about the epidemiology of RSV in the Middle East and North Africa (MENA) region. Therefore, we systematically searched four databases; Embase, Medline, Scopus, and Cochrane databases from 2001 to 2019 to collect all the information related to the RSV prevalence, genotype distribution, and seasonality in children in MENA region. Our search strategy identified 598 studies, of which 83 met our inclusion criteria, which cover the past 19 years (2000–2019). Odds ratio (OR) and confidence interval (CI) were calculated to measure the association between RSV prevalence, gender, and age distribution. An overall prevalence of 24.4% (n = 17,106/69,981) of respiratory infections was recorded for RSV. The highest RSV prevalence was reported in Jordan (64%, during 2006–2007) and Israel (56%, 2005–2006). RSV A subgroup was more prevalent (62.9%; OR = 2.9, 95%CI = 2.64–3.13) than RSV B. RSV was most prevalent in children who were less than 12 months old (68.6%; OR = 4.7, 95%CI = 2.6–8.6) and was higher in males (59.6%; OR = 2.17, 95%CI = 1.2–3.8) than in female infants. Finally, the highest prevalence was recorded during winter seasons in all countries, except for Pakistan. RSV prevalence in the MENA region is comparable with the global one (24.4% vs. 22%). This first comprehensive report about RSV prevalence in the MENA region and our data should be important to guide vaccine introduction decisions and future evaluation. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Diagnostics and Management of Respiratory Virus Infections)

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