Evolution and Ecology of Influenza A Viruses

Yoon, Sun‐Woo; Webby, Richard J.; Webster, Robert G.

doi:10.1007/82_2014_396

Cited by 279 publications

(298 citation statements)

References 138 publications

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“…Despite a certain level of host specificity, many interspecies influenza A virus transmission events have been documented (33). In that context, pigs are an important natural host for IAV and are closely associated with the ecology and evolution of IAV (33).…”

Section: Discussionmentioning

confidence: 99%

“…In that context, pigs are an important natural host for IAV and are closely associated with the ecology and evolution of IAV (33).…”

Section: Discussionmentioning

confidence: 99%

“…Globally, established strains of IAV in pigs are of three main subtypes: H1N1, H1N2, and H3N2 (1,33). Nevertheless, H3N1 viruses resulting from the reassortment between swine viruses (14,35,36) or from interspecies transmission and reassortment (2,37,38) have been detected previously.…”

Section: Discussionmentioning

confidence: 99%

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Novel Reassortant Human-Like H3N2 and H3N1 Influenza A Viruses Detected in Pigs Are Virulent and Antigenically Distinct from Swine Viruses Endemic to the United States

Rajão

Gauger

Anderson

et al. 2015

J Virol

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Human-like swine H3 influenza A viruses (IAV) were detected by the USDA surveillance system. We characterized two novel swine human-like H3N2 and H3N1 viruses with hemagglutinin (HA) genes similar to those in human seasonal H3 strains and internal genes closely related to those of 2009 H1N1 pandemic viruses. The H3N2 neuraminidase (NA) was of the contemporary human N2 lineage, while the H3N1 NA was of the classical swine N1 lineage. Both viruses were antigenically distant from swine H3 viruses that circulate in the United States and from swine vaccine strains and also showed antigenic drift from human seasonal H3N2 viruses. Their pathogenicity and transmission in pigs were compared to those of a human H3N2 virus with a common HA ancestry. Both swine human-like H3 viruses efficiently infected pigs and were transmitted to indirect contacts, whereas the human H3N2 virus did so much less efficiently. To evaluate the role of genes from the swine isolates in their pathogenesis, reverse genetics-generated reassortants between the swine human-like H3N1 virus and the seasonal human H3N2 virus were tested in pigs. The contribution of the gene segments to virulence was complex, with the swine HA and internal genes showing effects in vivo. The experimental infections indicate that these novel H3 viruses are virulent and can sustain onward transmission in pigs, and the naturally occurring mutations in the HA were associated with antigenic divergence from H3 IAV from humans and swine. Consequently, these viruses could have a significant impact on the swine industry if they were to cause more widespread outbreaks, and the potential risk of these emerging swine IAV to humans should be considered. IMPORTANCE Pigs are important hosts in the evolution of influenza A viruses (IAV). Human-to-swine transmissions of IAV have resulted in the circulation of reassortant viruses containing human-origin genes in pigs, greatly contributing to the diversity of IAV in swine worldwide. New human-like H3N2 and H3N1 viruses that contain a mix of human and swine gene segments were recently detected by the USDA surveillance system. The human-like viruses efficiently infected pigs and resulted in onward airborne transmission, likely due to the multiple changes identified between human and swine H3 viruses. The human-like swine viruses are distinct from contemporary U.S. H3 swine viruses and from the strains used in swine vaccines, which could have a significant impact on the swine industry due to a lack of population immunity. Additionally, public health experts should consider an appropriate assessment of the risk of these emerging swine H3 viruses for the human population.

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Section: Discussionmentioning

confidence: 99%

“…In that context, pigs are an important natural host for IAV and are closely associated with the ecology and evolution of IAV (33).…”

Section: Discussionmentioning

confidence: 99%

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Novel Reassortant Human-Like H3N2 and H3N1 Influenza A Viruses Detected in Pigs Are Virulent and Antigenically Distinct from Swine Viruses Endemic to the United States

Rajão

Gauger

Anderson

et al. 2015

J Virol

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“…IAVs are genetically diverse, with new strains rapidly emerging by point mutations introduced by the low-fidelity viral RNA replicase (potentially resulting in antigenic drift if changes occur in the HA and/or NA coding sequences and affect important antigenic epitopes) or by genetic reassortment of genomic segments (potentially leading to antigenic shift if antigenically distant HA and NA segments are incorporated). Minor and major antigenic changes in the HA and NA proteins of circulating IAV are important driving forces for the emergence of new strains causing epidemics or even major pandemics (Neumann et al, 2009;Peng et al, 2014;Smith et al, 2009;Yoon et al, 2014). Based on their antigenic properties, HA and NA proteins are classified into different types (H1-18 and N1-11) including those of the recently isolated bat-origin IAV (H17N10 and H18N11) (Tong et al, 2012(Tong et al, , 2013.…”

Section: Introductionmentioning

confidence: 99%

The PB1 segment of an influenza A virus H1N1 2009pdm isolate enhances the replication efficiency of specific influenza vaccine strains in cell culture and embryonated eggs

Mostafa

Kanrai

Ziebuhr

et al. 2016

Journal of General Virology

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Influenza vaccine strains (IVSs) contain the haemagglutinin (HA) and neuraminidase (NA) genome segments of relevant circulating strains in the genetic background of influenza A/ PR/8/1934 virus (PR8). Previous work has shown that the nature of the PB1 segment may be a limiting factor for the efficient production of IVSs. Here, we showed that the PB1 segment (PB1 Gi ) from the 2009 pandemic influenza A virus (IAV) A/Giessen/06/2009 (Gi wt, H1N1pdm) may help to resolve (some of) these limitations. We produced a set of recombinant PR8-derived viruses that contained (i) the HA and NA segments from representative IAV strains (H3N2, H5N1, H7N9, H9N2); (ii) the PB1 segment from PR8 or Gi wt, respectively; and (iii) the remaining five genome segments from PR8. Viruses containing the PB1 Gi segment, together with the heterologous HA/NA segments and five PR8 segments (5+2+1), replicated to higher titres compared with their 6+2 counterparts containing six PR8 segments and the equivalent heterologous HA/NA segments. Compared with PB1 PR8 -containing IVSs, viruses with the PB1 Gi segment replicated to higher or similar titres in both cell culture and embryonated eggs, most profoundly IVSs of the H5N1 and H7N9 subtype, which are known to grow poorly in these systems. IVSs containing either the PB1 Gi or the cognate PB1 segment of the respective specific HA/NA donor strain showed enhanced or similar virus replication levels. This study suggests that substitution of PB1 PR8 with the PB1 Gi segment may greatly improve the large-scale production of PR8-derived IVSs, especially of those known to replicate poorly in vitro. INTRODUCTIONInfluenza viruses belong to the family Orthomyxoviridae and are classified into three genera termed Influenza virus A, B and C. Among these, influenza A viruses (IAVs) pose the greatest threat to human and animal health. They contain eight segments of negative-sense ssRNA (Ritchey et al., 1976;Shaw & Palese, 2013). The eight genomic segments encode at least 10 viral proteins, comprising the three subunits of the viral RNA polymerase complex [polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1) and polymerase acidic protein (PA)], the surface glycoproteins [haemagglutinin (HA) and neuraminidase (NA)], the nucleoprotein (NP), the matrix protein (M1), the ion channel protein (M2), the non-structural protein 1 (NS1) and the nuclear export protein (NEP). IAVs are genetically diverse, with new strains rapidly emerging by point mutations introduced by the low-fidelity viral RNA replicase (potentially resulting in antigenic drift if changes occur in the HA and/or NA coding sequences and affect important antigenic epitopes) or by genetic reassortment of genomic segments (potentially leading to antigenic shift if antigenically distant HA and NA segments are incorporated). Minor and major antigenic changes in the HA and NA proteins of circulating IAV are important driving forces for the emergence of new strains causing epidemics or even major pandemics (Neumann et al., 2009;Peng et al., 2014;Smith...

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“…Avian influenza viruses (AIV) bearing 16 antigenic subtypes of hemagglutinin (HA) and 9 antigenic subtypes of neuraminidase (NA) have been isolated from waterfowl and shorebirds (3,4), and genetic evidence of H17N10 and H18N11 viruses has been found in bats (5). H3N8 influenza viruses are commonly found in wild birds but are not associated with disease; however, they have been associated with disease outbreaks in dogs (6), horses (7), pigs (8), donkeys (9), and most recently seals (10).…”

mentioning

confidence: 99%

A Single Dose of an Avian H3N8 Influenza Virus Vaccine Is Highly Immunogenic and Efficacious against a Recently Emerged Seal Influenza Virus in Mice and Ferrets

Baz

Paskel

Matsuoka

et al. 2015

J Virol

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H3N8 influenza viruses are a commonly found subtype in wild birds, usually causing mild or no disease in infected birds. However, they have crossed the species barrier and have been associated with outbreaks in dogs, pigs, donkeys, and seals and therefore pose a threat to humans. A live attenuated, cold-adapted (ca) H3N8 vaccine virus was generated by reverse genetics using the wild-type (wt) hemagglutinin ( We also analyzed human sera against the tl/TX/079/07 H3N8 avian influenza virus and observed low but detectable antibody reactivity in elderly subjects, suggesting that older H3N2 influenza viruses confer some cross-reactive antibody. The latter observation was confirmed in a ferret study. The safety, immunogenicity, and efficacy of the tl/TX/079/07 ca vaccine in mice and ferrets support further evaluation of this vaccine in humans for use in the event of transmission of an H3N8 avian influenza virus to humans. The human and ferret serology data suggest that a single dose of the vaccine may be sufficient in older subjects. IMPORTANCEAlthough natural infection of humans with an avian H3N8 influenza virus has not yet been reported, this influenza virus subtype has already crossed the species barrier and productively infected mammals. Pandemic preparedness is an important public health priority. Therefore, we generated a live attenuated avian H3N8 vaccine candidate and demonstrated that a single dose of the vaccine was highly immunogenic and protected mice and ferrets against homologous and heterologous H3N8 avian viruses. Influenza is an important disease in humans and animals. Influenza A viruses can cross the species barriers intact or following reassortment and have the potential to cause devastating pandemics in humans (1). Pandemic preparedness for influenza has generally been focused on highly pathogenic H5 and H7 avian influenza viruses. However, it is impossible to predict when and where an influenza pandemic will appear, how severe it will be, and which subtype of influenza will emerge as a pandemic strain. Several influenza viruses bearing novel viral gene segments from an animal source have arisen in humans and animals. An example of such an event that underscores the need to consider all influenza virus subtypes was the emergence of the novel H1N1 influenza virus in 2009 despite the ongoing circulation of seasonal H1N1 viruses (2).Avian influenza viruses (AIV) bearing 16 antigenic subtypes of hemagglutinin (HA) and 9 antigenic subtypes of neuraminidase (NA) have been isolated from waterfowl and shorebirds (3, 4), and genetic evidence of H17N10 and H18N11 viruses has been found in bats (5). H3N8 influenza viruses are commonly found in wild birds but are not associated with disease; however, they have been associated with disease outbreaks in dogs (6), horses (7), pigs (8), donkeys (9), and most recently seals (10). Although there have been no known avian H3N8 human cases to date, infections in other mammalian species highlight the ability of this influenza virus subtype to cross the species ...

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Evolution and Ecology of Influenza A Viruses

Cited by 279 publications

References 138 publications

Novel Reassortant Human-Like H3N2 and H3N1 Influenza A Viruses Detected in Pigs Are Virulent and Antigenically Distinct from Swine Viruses Endemic to the United States

Novel Reassortant Human-Like H3N2 and H3N1 Influenza A Viruses Detected in Pigs Are Virulent and Antigenically Distinct from Swine Viruses Endemic to the United States

The PB1 segment of an influenza A virus H1N1 2009pdm isolate enhances the replication efficiency of specific influenza vaccine strains in cell culture and embryonated eggs

A Single Dose of an Avian H3N8 Influenza Virus Vaccine Is Highly Immunogenic and Efficacious against a Recently Emerged Seal Influenza Virus in Mice and Ferrets

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