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Viruses
Special Issues
Evolution and Epidemiology of Influenza Virus
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Evolution and Epidemiology of Influenza Virus

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

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 17918

Special Issue Editors

Dr. Samantha Lycett

E-Mail Website
Guest Editor
Roslin Institute, University of Edinburgh, Midlothian, UK
Interests: evolution and epidemiology of viruses; human, swine and avian influenza viruses; phylodynamics and phylogeography, zoonotic potential, cross species transmissions, reassortments
Prof. Dr. Paul Digard

E-Mail Website
Guest Editor
Roslin Institute, University of Edinburgh, Midlothian, UK
Interests: molecular and cellular biology of influenza virus replication; the basis of virus pathogenesis and host range; identifying cellular pathways and viral elements involved in genome trafficking and virus assembly; viral RNA synthesis machinery and its role in setting host range; identifying novel virus polypeptides; translational studies on antiviral drug development and virus control measures

Special Issue Information

Dear colleagues,

There have been four human influenza A pandemics in just over 100 years: 1918, 1958, 1968, and 2009, of subtypes H1, H2 and H3. These trace at least some of their origins to animal sources, and back into the avian reservoir. To understand the evolutionary history of influenza viruses, and gain insights into what might happen next, studies into their diversity (types, subtypes, genome constellations, clades), circulation, spill over, dynamics in populations, replication, transmission, pathogenesis and selective advantages in avian and mammalian species are important.  Additionally, every year, it is important to understand which variants and strains are circulating for both animal and human species. However, this year, with the COVID-19 pandemic and especially the social distancing restrictions, will this also affect the dynamics of influenza in the human population?

The purpose of this Special Issue is to bring together a series of articles (both reviews and original research) related to the evolution and epidemiology of influenza viruses. All things are interesting about this virus! From deep time evolution and speciation, through zoonoses, cross species transmissions and reassortments, to topics such as predicting influenza outbreaks, discovering new strains and finding mutations which alter virulence or transmissibility, there are many possible areas of interest. We welcome articles exploring theoretical and computational studies, as well as experimental and field studies.

Dr. Samantha Lycett
Prof. Paul Digard
Guest Editors

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

  • viral evolution
  • viral diversity
  • reassortment
  • epidemiology
  • human influenza
  • avian influenza
  • swine influenza
  • animal influenza
  • influenza transmission
  • cross species transmission
  • virulence
  • pathogenesis
  • strain dynamics
  • allele dynamics
  • phylodynamics
  • phylogeography
  • phylogenetics
  • within-host diversity

Published Papers (7 papers)

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Research

9 pages, 3369 KiB  
Communication
Phylogenetic and Phylogeographic Analysis of the Highly Pathogenic H5N6 Avian Influenza Virus in China
by Hanlin Liu, Changrong Wu, Zifeng Pang, Rui Zhao, Ming Liao and Hailiang Sun
Viruses 2022, 14(8), 1752; https://doi.org/10.3390/v14081752 - 11 Aug 2022
Cited by 4 | Viewed by 2328
Abstract
The clade 2.3.4.4b H5N8 avian influenza viruses (AIVs) have caused the loss of more than 33 million domestic poultry worldwide since January 2020. Novel H5N6 reassortants with hemagglutinin (HA) from clade 2.3.4.4b H5N8 AIVs are responsible for multiple human infections in China. Therefore, [...] Read more.
The clade 2.3.4.4b H5N8 avian influenza viruses (AIVs) have caused the loss of more than 33 million domestic poultry worldwide since January 2020. Novel H5N6 reassortants with hemagglutinin (HA) from clade 2.3.4.4b H5N8 AIVs are responsible for multiple human infections in China. Therefore, we conducted an epidemiological survey on waterfowl farms in Sichuan and Guangxi provinces and performed a comprehensive spatiotemporal analysis of H5N6 AIVs in China. At the nucleotide level, the H5N6 AIVs isolated in the present study exhibited high homology with the H5N6 AIVs that caused human infections. Demographic history indicates that clade 2.3.4.4b seemingly replaced clade 2.3.4.4h to become China’s predominant H5N6 AIV clade. Based on genomic diversity, we classified clade 2.3.4.4b H5N6 AIV into ten genotypes (2.3.4.4bG1–G10), of which the 2.3.4.4bG5 and G10 AIVs can cause human infections. Phylogeographic results suggest that Hong Kong and Jiangxi acted as important epicentres for clades 2.3.4.4b and 2.3.4.4h, respectively. Taken together, our study provides critical insight into the evolution and spread of H5N6 AIVs in China, which indicates that the novel 2.3.4.4b reassortants pose challenges for public health and poultry. Full article
(This article belongs to the Special Issue Evolution and Epidemiology of Influenza Virus)
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20 pages, 3523 KiB  
Article
Molecular Characterization and Pathogenesis of H6N6 Low Pathogenic Avian Influenza Viruses Isolated from Mallard Ducks (Anas platyrhynchos) in South Korea
by Kaliannan Durairaj, Thuy-Tien Thi Trinh, Su-Yeon Yun, Seon-Ju Yeo, Haan-Woo Sung and Hyun Park
Viruses 2022, 14(5), 1001; https://doi.org/10.3390/v14051001 - 08 May 2022
Cited by 4 | Viewed by 2299
Abstract
The subtype H6N6 has been identified worldwide following the increasing frequency of avian influenza viruses (AIVs). These AIVs also have the ability to bind to human-like receptors, thereby increasing the risk of animal-human transmission. In September 2019, an H6N6 avian influenza virus—KNU2019-48 (A/Mallard [...] Read more.
The subtype H6N6 has been identified worldwide following the increasing frequency of avian influenza viruses (AIVs). These AIVs also have the ability to bind to human-like receptors, thereby increasing the risk of animal-human transmission. In September 2019, an H6N6 avian influenza virus—KNU2019-48 (A/Mallard (Anas platyrhynchos)/South Korea/KNU 2019-48/2019(H6N6))—was isolated from Anas platyrhynchos in South Korea. Phylogenetic analysis results revealed that the hemagglutinin (HA) gene of this strain belongs to the Korean lineage, whereas the neuraminidase (NA) and polymerase basic protein 1 (PB1) genes belong to the Chinese lineage. Outstanding internal proteins such as PB2, polymerase acidic protein, nucleoprotein, matrix protein, and non-structural protein belong to the Vietnamese lineage. Additionally, a monobasic amino acid (PRIETR↓GLF) at the HA cleavage site; non-deletion of the stalk region (residue 59–69) in the NA gene; and E627 in the PB2 gene indicate that the KNU2019-48 isolate is a typical low-pathogenic avian influenza (LPAI) virus. The nucleotide sequence similarity analysis of HA revealed that the highest homology (97.18%) of this isolate is to that of A/duck/Jiangxi/01.14 NCJD125-P/2015(H6N6), and the amino acid sequence of NA (97.38%) is closely related to that of A/duck/Fujian/10.11_FZHX1045-C/2016 (H6N6). An in vitro analysis of the KNU2019-48 virus shows a virus titer of not more than 2.8 Log10 TCID 50/mL until 72 h post-infection, whereas in the lungs, the virus is detected at 3 dpi (days post-infection). The isolated KNU2019-48 (H6N6) strain is the first reported AIV in Korea, and the H6 subtype virus has co-circulated in China, Vietnam, and Korea for half a decade. Overall, our study demonstrates that Korean H6N6 strain PB1-S375N, PA-A404S, and S409N mutations are infectious in humans and might contribute to the enhanced pathogenicity of this strain. Therefore, we emphasize the importance of continuous and intensive surveillance of the H6N6 virus not only in Korea but also worldwide. Full article
(This article belongs to the Special Issue Evolution and Epidemiology of Influenza Virus)
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22 pages, 1754 KiB  
Article
Simulated Flock-Level Shedding Characteristics of Turkeys in Ten Thousand Bird Houses Infected with H7 Low Pathogenicity Avian Influenza Virus Strains
by Peter J. Bonney, Sasidhar Malladi, Amos Ssematimba, Kaitlyn M. St. Charles, Emily Walz, Marie R. Culhane, David A. Halvorson and Carol J. Cardona
Viruses 2021, 13(12), 2509; https://doi.org/10.3390/v13122509 - 14 Dec 2021
Viewed by 2140
Abstract
Understanding the amount of virus shed at the flock level by birds infected with low pathogenicity avian influenza virus (LPAIV) over time can help inform the type and timing of activities performed in response to a confirmed LPAIV-positive premises. To this end, we [...] Read more.
Understanding the amount of virus shed at the flock level by birds infected with low pathogenicity avian influenza virus (LPAIV) over time can help inform the type and timing of activities performed in response to a confirmed LPAIV-positive premises. To this end, we developed a mathematical model which allows us to estimate viral shedding by 10,000 turkey toms raised in commercial turkey production in the United States, and infected by H7 LPAIV strains. We simulated the amount of virus shed orally and from the cloaca over time, as well as the amount of virus in manure. In addition, we simulated the threshold cycle value (Ct) of pooled oropharyngeal swabs from birds in the infected flock tested by real-time reverse transcription polymerase chain reaction. The simulation model predicted that little to no shedding would occur once the highest threshold of seroconversion was reached. Substantial amounts of virus in manure (median 1.5×108 and 5.8×109; 50% egg infectious dose) were predicted at the peak. Lastly, the model results suggested that higher Ct values, indicating less viral shedding, are more likely to be observed later in the infection process as the flock approaches recovery. Full article
(This article belongs to the Special Issue Evolution and Epidemiology of Influenza Virus)
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7 pages, 2268 KiB  
Communication
Genetic Characterization of Novel H7Nx Low Pathogenic Avian Influenza Viruses from Wild Birds in South Korea during the Winter of 2020–2021
by Yu-Na Lee, Dong-Hun Lee, Jung-Hoon Kwon, Jae-In Shin, Seo Yun Hong, Ra Mi Cha, Yoon-Gi Baek, Eun-Kyoung Lee, Mingeun Sagong, Gyeong-Beum Heo, Kwang-Nyeong Lee and Youn-Jeong Lee
Viruses 2021, 13(11), 2274; https://doi.org/10.3390/v13112274 - 13 Nov 2021
Cited by 2 | Viewed by 1999
Abstract
Zoonotic infection with avian influenza viruses (AIVs) of subtype H7, such as H7N9 and H7N4, has raised concerns worldwide. During the winter of 2020–2021, five novel H7 low pathogenic AIVs (LPAIVs) containing different neuraminidase (NA) subtypes, including two H7N3, an H7N8, and two [...] Read more.
Zoonotic infection with avian influenza viruses (AIVs) of subtype H7, such as H7N9 and H7N4, has raised concerns worldwide. During the winter of 2020–2021, five novel H7 low pathogenic AIVs (LPAIVs) containing different neuraminidase (NA) subtypes, including two H7N3, an H7N8, and two H7N9, were detected in wild bird feces in South Korea. Complete genome sequencing and phylogenetic analysis showed that the novel H7Nx AIVs were reassortants containing two gene segments (hemagglutinin (HA) and matrix) that were related to the zoonotic Jiangsu–Cambodian H7 viruses causing zoonotic infection and six gene segments originating from LPAIVs circulating in migratory birds in Eurasia. A genomic constellation analysis demonstrated that all H7 isolates contained a mix of gene segments from different viruses, indicating that multiple reassortment occurred. The well-known mammalian adaptive substitution (E627K and D701N) in PB2 was not detected in any of these isolates. The detection of multiple reassortant H7Nx AIVs in wild birds highlights the need for intensive surveillance in both wild birds and poultry in Eurasia. Full article
(This article belongs to the Special Issue Evolution and Epidemiology of Influenza Virus)
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22 pages, 10463 KiB  
Article
Genotypic Variants of Pandemic H1N1 Influenza A Viruses Isolated from Severe Acute Respiratory Infections in Ukraine during the 2015/16 Influenza Season
by Oksana Zolotarova, Anna Fesenko, Olga Holubka, Larysa Radchenko, Eric Bortz, Iryna Budzanivska and Alla Mironenko
Viruses 2021, 13(11), 2125; https://doi.org/10.3390/v13112125 - 21 Oct 2021
Cited by 1 | Viewed by 2066
Abstract
Human type A influenza viruses A(H1N1)pdm09 have caused seasonal epidemics of influenza since the 2009–2010 pandemic. A(H1N1)pdm09 viruses had a leading role in the severe epidemic season of 2015/16 in the Northern Hemisphere and caused a high incidence of acute respiratory infection (ARI) [...] Read more.
Human type A influenza viruses A(H1N1)pdm09 have caused seasonal epidemics of influenza since the 2009–2010 pandemic. A(H1N1)pdm09 viruses had a leading role in the severe epidemic season of 2015/16 in the Northern Hemisphere and caused a high incidence of acute respiratory infection (ARI) in Ukraine. Serious complications of influenza-associated severe ARI (SARI) were observed in the very young and individuals at increased risk, and 391 fatal cases occurred in the 2015/16 epidemic season. We analyzed the genetic changes in the genomes of A(H1N1)pdm09 influenza viruses isolated from SARI cases in Ukraine during the 2015/16 season. The viral hemagglutinin (HA) fell in H1 group 6B.1 for all but four isolates, with known mutations affecting glycosylation, the Sa antigenic site (S162N in all 6B.1 isolates), or virulence (D222G/N in two isolates). Other mutations occurred in antigenic site Ca (A141P and S236P), and a subgroup of four strains were in group 6B.2, with potential alterations to antigenicity in A(H1N1)pdm09 viruses circulating in 2015/16 in Ukraine. A cluster of Ukrainian isolates exhibited novel D2E and N48S mutations in the RNA binding domain, and E125D in the effector domain, of immune evasion nonstructural protein 1 (NS1). The diverse spectrum of amino-acid substitutions in HA, NS1, and other viral proteins including nucleoprotein (NP) and the polymerase complex suggested the concurrent circulation of multiple lineages of A(H1N1)pdm09 influenza viruses in the human population in Ukraine, a country with low vaccination coverage, complicating public health measures against influenza. Full article
(This article belongs to the Special Issue Evolution and Epidemiology of Influenza Virus)
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15 pages, 2407 KiB  
Article
Characterizing the Countrywide Epidemic Spread of Influenza A(H1N1)pdm09 Virus in Kenya between 2009 and 2018
by D. Collins Owuor, Zaydah R. de Laurent, Gilbert K. Kikwai, Lillian M. Mayieka, Melvin Ochieng, Nicola F. Müller, Nancy A. Otieno, Gideon O. Emukule, Elizabeth A. Hunsperger, Rebecca Garten, John R. Barnes, Sandra S. Chaves, D. James Nokes and Charles N. Agoti
Viruses 2021, 13(10), 1956; https://doi.org/10.3390/v13101956 - 29 Sep 2021
Cited by 2 | Viewed by 2929
Abstract
The spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data are lacking. We isolated, sequenced, and analyzed 383 A(H1N1)pdm09 viral genomes from hospitalized patients between 2009 and 2018 [...] Read more.
The spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data are lacking. We isolated, sequenced, and analyzed 383 A(H1N1)pdm09 viral genomes from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods. The transmission dynamics of A(H1N1)pdm09 virus in Kenya were characterized by (i) multiple virus introductions into Kenya over the study period, although only a few of those introductions instigated local seasonal epidemics that then established local transmission clusters, (ii) persistence of transmission clusters over several epidemic seasons across the country, (iii) seasonal fluctuations in effective reproduction number (Re) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres, (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009–2011 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012–2017, and (v) virus spread across Kenya. Considerable influenza virus diversity circulated within Kenya, including persistent viral lineages that were unique to the country, which may have been capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle-income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions. Full article
(This article belongs to the Special Issue Evolution and Epidemiology of Influenza Virus)
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27 pages, 5745 KiB  
Article
Genetic and Antigenic Evolution of European Swine Influenza A Viruses of HA-1C (Avian-Like) and HA-1B (Human-Like) Lineages in France from 2000 to 2018
by Amélie Chastagner, Séverine Hervé, Stéphane Quéguiner, Edouard Hirchaud, Pierrick Lucas, Stéphane Gorin, Véronique Béven, Nicolas Barbier, Céline Deblanc, Yannick Blanchard and Gaëlle Simon
Viruses 2020, 12(11), 1304; https://doi.org/10.3390/v12111304 - 13 Nov 2020
Cited by 7 | Viewed by 2337
Abstract
This study evaluated the genetic and antigenic evolution of swine influenza A viruses (swIAV) of the two main enzootic H1 lineages, i.e., HA-1C (H1av) and -1B (H1hu), circulating in France between 2000 and 2018. SwIAV RNAs extracted from 1220 [...] Read more.
This study evaluated the genetic and antigenic evolution of swine influenza A viruses (swIAV) of the two main enzootic H1 lineages, i.e., HA-1C (H1av) and -1B (H1hu), circulating in France between 2000 and 2018. SwIAV RNAs extracted from 1220 swine nasal swabs were hemagglutinin/neuraminidase (HA/NA) subtyped by RT-qPCRs, and 293 virus isolates were sequenced. In addition, 146 H1avNy and 105 H1huNy strains were submitted to hemagglutination inhibition tests. H1avN1 (66.5%) and H1huN2 (25.4%) subtypes were predominant. Most H1 strains belonged to HA-1C.2.1 or -1B.1.2.3 clades, but HA-1C.2, -1C.2.2, -1C.2.3, -1B.1.1, and -1B.1.2.1 clades were also detected sporadically. Within HA-1B.1.2.3 clade, a group of strains named “Δ146-147” harbored several amino acid mutations and a double deletion in HA, that led to a marked antigenic drift. Phylogenetic analyses revealed that internal segments belonged mainly to the “Eurasian avian-like lineage”, with two distinct genogroups for the M segment. In total, 17 distinct genotypes were identified within the study period. Reassortments of H1av/H1hu strains with H1N1pdm virus were rarely evidenced until 2018. Analysis of amino acid sequences predicted a variability in length of PB1-F2 and PA-X proteins and identified the appearance of several mutations in PB1, PB1-F2, PA, NP and NS1 proteins that could be linked to virulence, while markers for antiviral resistance were identified in N1 and N2. Altogether, diversity and evolution of swIAV recall the importance of disrupting the spreading of swIAV within and between pig herds, as well as IAV inter-species transmissions. Full article
(This article belongs to the Special Issue Evolution and Epidemiology of Influenza Virus)
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