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Viruses
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Molecular Biology of Influenza Viruses
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Molecular Biology of Influenza Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (30 December 2022) | Viewed by 13677

Special Issue Editor

Prof. Dr. Jihui Ping

E-Mail Website
Guest Editor
Institute of Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
Interests: influenza A virus; evolution and variation of influenza viurs; cross-species infection and transmission; molecular pathogenesis; high yield influenza vaccine virus development

Special Issue Information

Dear Colleagues,

The influenza viruses belong to the family Orthomyxoviridae and contain a genome composed of eight segments of single-stranded, negative sense RNA that each encodes one or two viral proteins. Four influenza genera, influenza A, B, C, and D, are classified based on antigenic differences in the NP and M genes. Symptoms associated with influenza virus infection vary from a mild respiratory disease to severe and in some cases lethal pneumonia. The WHO estimates that annual epidemics of influenza result in approximately 1 billion infections, 3–5 million cases of severe illness, and 300,000–500,000 deaths. The most severe influenza pandemic, the “Spanish flu” in 1918, resulted in ~50 million deaths worldwide. Ideally, influenza A viruses have relatively strict host restrictions; although very rare, subtype H5, H7, and even H9 virus have crossed the species barrier to produce sporadic infection of humans and resulted in revere economic losses and public health concern.

Therefore, there is a major need to better understand the molecular biology of influenza virus infections to development new and more effective antiviral strategies to prevent influenza outbreaks.  In this Special Issue, original scientific research on (but not limited to) the following topics are welcome:

1) Genetic and antigenic evolution of influenza viruses;

2) Epidemiology and ecology of influenza viruses;

3) Cross-species transmission and pathogenesis;

4) Antiviral immune response;

5) Diagnosis and prevention.

Prof. Dr. Jihui Ping
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • influenza virus
  • reassortment and variation
  • evolution
  • host adapting molecular markers
  • cross-species transmission
  • antigenic drift and shift

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Published Papers (5 papers)

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Research

18 pages, 2494 KiB  
Article
Analysis of Avian Influenza (H5N5) Viruses Isolated in the Southwestern European Part of the Russian Federation in 2020–2021
by Nikolay Zinyakov, Artem Andriyasov, Pavel Zhestkov, Anton Kozlov, Zoya Nikonova, Evgeniya Ovchinnikova, Alena Grekhneva, Lidiya Shcherbakova, Dmitriy Andreychuk, Alexander Sprygin, Larisa Prokhvatilova and Iliya Chvala
Viruses 2022, 14(12), 2725; https://doi.org/10.3390/v14122725 - 6 Dec 2022
Cited by 5 | Viewed by 2672
Abstract
In 2021, several isolates of the H5N5 avian influenza virus (AIV) were detected in Europe and the Russian Federation, which differed from those detected in 2020. Genetic analysis revealed a relationship between the highly pathogenic avian influenza H5N5 subtype, detected in Europe, and [...] Read more.
In 2021, several isolates of the H5N5 avian influenza virus (AIV) were detected in Europe and the Russian Federation, which differed from those detected in 2020. Genetic analysis revealed a relationship between the highly pathogenic avian influenza H5N5 subtype, detected in Europe, and some isolates detected in the Russian Federation territory in 2020–2021: it was shown that both originated in the Caspian Sea regions around the autumn of 2020. The appearance of H5N5 subtype viruses in the spring of 2021 in Europe and the Russian Federation was not associated with the mass migration of birds from Africa. The results of the analysis revealed the presence of a deletion in the stem of a neuraminidase between bp 139 and 204 (open reading frame). It has been shown that AIVs of the H5N5 subtype are capable of long-term circulation in wild bird populations with the possibility of reassortment. The results also highlighted the need for careful monitoring of the circulation of AIVs in the Caspian Sea region, the role of which, in the preservation and emergence of new antigenic variants of such viruses in Eurasia, is currently underestimated. Full article
(This article belongs to the Special Issue Molecular Biology of Influenza Viruses)
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16 pages, 2160 KiB  
Article
Evolutionary Dynamics of Whole-Genome Influenza A/H3N2 Viruses Isolated in Myanmar from 2015 to 2019
by Wint Wint Phyu, Reiko Saito, Yadanar Kyaw, Nay Lin, Su Mon Kyaw Win, Nay Chi Win, Lasham Di Ja, Khin Thu Zar Htwe, Thin Zar Aung, Htay Htay Tin, Eh Htoo Pe, Irina Chon, Keita Wagatsuma and Hisami Watanabe
Viruses 2022, 14(11), 2414; https://doi.org/10.3390/v14112414 - 31 Oct 2022
Cited by 9 | Viewed by 2534
Abstract
This study aimed to analyze the genetic and evolutionary characteristics of the influenza A/H3N2 viruses circulating in Myanmar from 2015 to 2019. Whole genomes from 79 virus isolates were amplified using real-time polymerase chain reaction and successfully sequenced using the Illumina iSeq100 platforms. [...] Read more.
This study aimed to analyze the genetic and evolutionary characteristics of the influenza A/H3N2 viruses circulating in Myanmar from 2015 to 2019. Whole genomes from 79 virus isolates were amplified using real-time polymerase chain reaction and successfully sequenced using the Illumina iSeq100 platforms. Eight individual phylogenetic trees were retrieved for each segment along with those of the World Health Organization (WHO)-recommended Southern Hemisphere vaccine strains for the respective years. Based on the WHO clades classification, the A/H3N2 strains in Myanmar from 2015 to 2019 collectively belonged to clade 3c.2. These strains were further defined based on hemagglutinin substitutions as follows: clade 3C.2a (n = 39), 3C.2a1 (n = 2), and 3C.2a1b (n = 38). Genetic analysis revealed that the Myanmar strains differed from the Southern Hemisphere vaccine strains each year, indicating that the vaccine strains did not match the circulating strains. The highest rates of nucleotide substitution were estimated for hemagglutinin (3.37 × 10−3 substitutions/site/year) and neuraminidase (2.89 × 10−3 substitutions/site/year). The lowest rate was for non-structural protein segments (4.19 × 10−5 substitutions/site/year). The substantial genetic diversity that was revealed improved phylogenetic classification. This information will be particularly relevant for improving vaccine strain selection. Full article
(This article belongs to the Special Issue Molecular Biology of Influenza Viruses)
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16 pages, 1661 KiB  
Article
Predicting Egg Passage Adaptations to Design Better Vaccines for the H3N2 Influenza Virus
by Yunsong Liu, Hui Chen, Wenyuan Duan, Xinyi Zhang, Xionglei He, Rasmus Nielsen, Liang Ma and Weiwei Zhai
Viruses 2022, 14(9), 2065; https://doi.org/10.3390/v14092065 - 17 Sep 2022
Cited by 1 | Viewed by 2535
Abstract
Seasonal H3N2 influenza evolves rapidly, leading to an extremely poor vaccine efficacy. Substitutions employed during vaccine production using embryonated eggs (i.e., egg passage adaptation) contribute to the poor vaccine efficacy (VE), but the evolutionary mechanism remains elusive. Using an unprecedented number of hemagglutinin [...] Read more.
Seasonal H3N2 influenza evolves rapidly, leading to an extremely poor vaccine efficacy. Substitutions employed during vaccine production using embryonated eggs (i.e., egg passage adaptation) contribute to the poor vaccine efficacy (VE), but the evolutionary mechanism remains elusive. Using an unprecedented number of hemagglutinin sequences (n = 89,853), we found that the fitness landscape of passage adaptation is dominated by pervasive epistasis between two leading residues (186 and 194) and multiple other positions. Convergent evolutionary paths driven by strong epistasis explain most of the variation in VE, which has resulted in extremely poor vaccines for the past decade. Leveraging the unique fitness landscape, we developed a novel machine learning model that can predict egg passage substitutions for any candidate vaccine strain before the passage experiment, providing a unique opportunity for the selection of optimal vaccine viruses. Our study presents one of the most comprehensive characterizations of the fitness landscape of a virus and demonstrates that evolutionary trajectories can be harnessed for improved influenza vaccines. Full article
(This article belongs to the Special Issue Molecular Biology of Influenza Viruses)
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14 pages, 2287 KiB  
Article
ARNT Inhibits H5N1 Influenza A Virus Replication by Interacting with the PA Protein
by Huapeng Feng, Zeng Wang, Pengyang Zhu, Li Wu, Jianzhong Shi, Yanbing Li, Jianhong Shu, Yulong He and Huihui Kong
Viruses 2022, 14(7), 1347; https://doi.org/10.3390/v14071347 - 21 Jun 2022
Cited by 2 | Viewed by 2650
Abstract
Increasing evidence suggests that the polymerase acidic (PA) protein of influenza A viruses plays an important role in viral replication and pathogenicity. However, information regarding the interaction(s) of host factors with PA is scarce. By using a yeast two-hybrid screen, we identified a [...] Read more.
Increasing evidence suggests that the polymerase acidic (PA) protein of influenza A viruses plays an important role in viral replication and pathogenicity. However, information regarding the interaction(s) of host factors with PA is scarce. By using a yeast two-hybrid screen, we identified a novel host factor, aryl hydrocarbon receptor nuclear translocator (ARNT), that interacts with the PA protein of the H5N1 virus. The interaction between PA and human ARNT was confirmed by co-immunoprecipitation and immunofluorescence microscopy. Moreover, overexpression of ARNT downregulated the polymerase activity and inhibited virus propagation, whereas knockdown of ARNT significantly increased the polymerase activity and virus replication. Mechanistically, overexpression of ARNT resulted in the accumulation of PA protein in the nucleus and inhibited both the replication and transcription of the viral genome. Interaction domain mapping revealed that the bHLH/PAS domain of ARNT mainly interacted with the C-terminal domain of PA. Together, our results demonstrate that ARNT inhibits the replication of the H5N1 virus and could be a target for the development of therapeutic strategies against H5N1 influenza viruses. Full article
(This article belongs to the Special Issue Molecular Biology of Influenza Viruses)
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17 pages, 4963 KiB  
Article
D2I and F9Y Mutations in the NS1 Protein of Influenza A Virus Affect Viral Replication via Regulating Host Innate Immune Responses
by Mengqi Yu, Yanna Guo, Lingcai Zhao, Yuanlu Lu, Qingzheng Liu, Yinjing Li, Lulu Deng, Zhiyu Shi, Haifeng Wang, Samar Dankar and Jihui Ping
Viruses 2022, 14(6), 1206; https://doi.org/10.3390/v14061206 - 1 Jun 2022
Cited by 4 | Viewed by 2389
Abstract
Influenza A viruses (IAV) modulate host antiviral responses to promote viral growth and pathogenicity. The non-structural (NS1) protein of influenza A virus has played an indispensable role in the inhibition of host immune responses, especially in limiting interferon (IFN) production. In this study, [...] Read more.
Influenza A viruses (IAV) modulate host antiviral responses to promote viral growth and pathogenicity. The non-structural (NS1) protein of influenza A virus has played an indispensable role in the inhibition of host immune responses, especially in limiting interferon (IFN) production. In this study, random site mutations were introduced into the NS1 gene of A/WSN/1933 (WSN, H1N1) via an error prone PCR to construct a random mutant plasmid library. The NS1 random mutant virus library was generated by reverse genetics. To screen out the unidentified NS1 functional mutants, the library viruses were lung-to-lung passaged in mice and individual plaques were picked from the fourth passage in mice lungs. Sanger sequencing revealed that eight different kinds of mutations in the NS1 gene were obtained from the passaged library virus. We found that the NS1 F9Y mutation significantly enhanced viral growth in vitro (MDCK and A549 cells) and in vivo (BALB/c mice) as well as increased virulence in mice. The NS1 D2I mutation attenuated the viral replication and pathogenicity in both in vitro and in vivo models. Further studies demonstrated that the NS1 F9Y mutant virus exhibited systematic and selective inhibition of cytokine responses as well as inhibited the expression of IFN. In addition, the expression levels of innate immunity-related cytokines were significantly up-regulated after the rNS1 D2I virus infected A549 cells. Collectively, our results revealed that the two mutations in the N-terminal of the NS1 protein could alter the viral properties of IAV and provide additional evidence that the NS1 protein is a critical virulence factor. The two characterized NS1 mutations may serve as potential targets for antiviral drugs as well as attenuated vaccine development. Full article
(This article belongs to the Special Issue Molecular Biology of Influenza Viruses)
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