Pathogenicity and transmission of a swine influenza A(H6N6) virus

Sun, Hailiang; Kaplan, Bryan S.; Guan, Minhui; Zhang, Guihong; Ye, Jianqiang; Li, Long; Blackmon, Sherry; Yang, Chun Kai; Chiang, Meng Jung; Xie, Hang; Zhao, Nan; Cooley, Jim; Smith, David F.; Liao, Ming; Cardona, Carol J.; Li, Lei; Wang, George Peng; Webby, Richard J.; Wan, Xiu Feng

doi:10.1038/emi.2017.3

Cited by 22 publications

(18 citation statements)

References 53 publications

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“…The internal genes of the influenza A(H1N1) pdm09 virus, which is prevalent in swine worldwide, increases the replication efficiency of H6N6 IAV in the lower respiratory tract of ferrets but not its transmissibility between ferrets. Experiments have shown that the virus has limited transmissibility through direct contact or through inhalation of infectious aerosolised droplets [ 81 ]. The aims of the study conducted by Sun et al were to understand the impacts of mutations in HA of the endemic H6N6 virus on its receptor-binding properties and also to assess the transmission potential and potential risks posed by reassortants of H6N6 with the A(H1N1)pdm09 virus.…”

Section: H6nx Viruses In Mammalian Species and Zoonotic Infectionmentioning

confidence: 99%

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The Evolution, Spread and Global Threat of H6Nx Avian Influenza Viruses

Everest

Hill

Daines

et al. 2020

Viruses

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Avian influenza viruses of the subtype H6Nx are being detected globally with increasing frequency. Some H6Nx lineages are becoming enzootic in Asian poultry and sporadic incursions into European poultry are occurring more frequently. H6Nx viruses that contain mammalian adaptation motifs pose a zoonotic threat and have caused human cases. Although currently understudied globally, H6Nx avian influenza viruses pose a substantial threat to both poultry and human health. In this review we examine the current state of knowledge of H6Nx viruses including their global distribution, tropism, transmission routes and human health risk.

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Section: H6nx Viruses In Mammalian Species and Zoonotic Infectionmentioning

confidence: 99%

“…In 2010, a H6N6 virus emerged in southern China, and since then, has caused sporadic infections among swine, with the virus binding to both α2,6 (human-like) and α2,3 (avian-like) sialic acids [ 81 ].…”

Section: H6nx Viruses In Mammalian Species and Zoonotic Infectionmentioning

confidence: 99%

The Evolution, Spread and Global Threat of H6Nx Avian Influenza Viruses

Everest

Hill

Daines

et al. 2020

Viruses

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“…For example, four amino acid substitutions in the HA receptor binding sites and one in the polymerase complex protein basic polymerase 2 (PB2), enabled H5N1 avian IAV to transmit in ferrets through airborne droplets [16]. Mutations at HA residues 222 (alanine to valine) and 228 (glycine to serine) increased the receptor binding preference of H6N6 avian IAVs to SA2,6Gal [17]. In addition to glycan receptor binding preference, genetic constellation of RNP complex and adaptative mutations in RNP genes, including PB1, have been shown to affect the host and tissue tropisms of IAVs [18–21].…”

Section: Introductionmentioning

confidence: 99%

Tissue tropisms of avian influenza A viruses affect their spillovers from wild birds to pigs

Zhang

Cummingham²,

et al. 2020

Preprint

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32Wild aquatic birds maintain a large genetically diverse pool of influenza A viruses (IAVs), which can be 33 transmitted to lower mammals and ultimately humans. Through phenotypic analyses, only a small set of 34 avian IAVs replicated well in the epithelial cells of swine upper respiratory tracts, and these viruses were 35 shown to infect and cause virus shedding in pigs. Such a phenotypic trait appears to emerge randomly and 36 are distributed among IAVs across multiple avian species, geographic and temporal orders, and is 37 determined not by receptor binding preference but other markers across genomic segments, such as those 38 in the ribonucleoprotein complex. This study demonstrates that phenotypic variants exist among avian 39 IAVs, only a few of which may result in viral shedding in pigs upon infection, providing opportunities for 40 these viruses to become pig adapted, thus posing a higher potential risk for creating novel variants or 41 detrimental reassortants within pig populations. 42 43 44 45 46 47 Author Summary 49Having both avian-like receptors and human-like α2,6-linked sialic acid receptors, swine serve as a 50 "mixing vessel" for generating human influenza pandemic strains. All HA subtypes of IAVs can infect 51 swine; however, only sporadic cases of avian IAVs are reported in domestic swine. The molecular 52 mechanisms affecting avian IAVs ability to infect swine are still not fully understood. Through 53 phenotypic analyses, this study suggested that tissue tropisms (i.e., in swine upper respiratory tracts) of 54 avian IAVs affect their spillovers from wild birds to pigs, and this phenotype was determined not by 55 receptor binding preference but by other markers across genomic segments, such as those in the 56 ribonucleoprotein complex. In addition, our results showed that such a phenotypic trait was sporadically 57 and randomly distributed among IAVs across multiple avian species, geographic and temporal orders. 58This study suggested an efficient way for risk assessment of avian IAVs, such as in evaluating their 59 potentials to be transmitted from avian to pigs. 60 61 Influenza A viruses (IAVs), a member in the Orthomyxoviridae family, are a negative single stranded 63 RNA virus with eight gene segments, encoding at least 11 proteins. The nomenclatures of IAVs are 64 determined based on antigenic properties of two surface glycoproteins, Hemagglutinin (HA) and 65 Neuraminidase (NA). To date, 18 HA subtypes and 11 NA subtypes have been identified [1, 2]. Besides 66 humans, pigs, dogs, and horses, IAVs have been recovered from variety of bird species, including at least 67 105 wild bird species of 26 different families [3]. Among wild birds, birds of wetlands and aquatic 68 environments such as the Anseriformes (particularly ducks, geese, and swans) and Charadriiformes 69 (particularly gulls, terns, and waders) constitute the major natural IAV reservoir [4]. They maintain a 70 large IAV genetic pool, which contributes to the appearance of new IAVs in other birds, lower mammals, 71 and ultima...

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“…Its ability to replicate well in mice without pre-adaptation was an early indication that these viruses could cause cross-species infection in mammals [13][14]. H6 subtypes have since been isolated from cases of respiratory illness in pigs [15][16] and dogs [17]. Serologic surveillance of humans revealed that veterinarians and agricultural workers exposed to H6 IAV-infected poultry could also become infected [18][19] and in May 2013 the first human infection with an avian influenza H6 subtype linked to respiratory illness was reported in Taiwan.…”

Section: Introductionmentioning

confidence: 99%

Continuing evolution of H6N2 influenza A virus in South African chickens and the implications for diagnosis and control

Abolnik¹,

Strydom

Rauff

et al. 2019

Preprint

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Background: The threat of poultry-origin H6 avian influenza viruses to human health emphasizes the importance of monitoring their evolution. South Africa’s H6N2 epidemic in chickens began in 2001 and two co-circulating antigenic sub-lineages of H6N2 could be distinguished from the outset. The true incidence and prevalence of H6N2 in the country has been difficult to determine, partly due to the continued use of an inactivated whole virus H6N2 vaccine and the inability to distinguish vaccinated from non-vaccinated birds on serology tests. In the present study, the complete genomes of twelve H6N2 viruses isolated from various farming systems between September 2015 and February 2019 in three major chicken-producing regions were analysed and a serological experiment was used to demonstrate the effects of antigenic mismatch in diagnostic tests. Results: Genetic drift in H6N2 continued and antigenic diversity in sub-lineage I is increasing; no sub-lineage II viruses were detected. Reassortment patterns indicated epidemiological connections between provinces as well as different farming systems, but there was no reassortment with wild bird or ostrich influenza viruses. The sequence mismatch between the official antigens used for hemagglutination inhibition (HI) testing and circulating field strains has increased steadily, and we demonstrated that these antigens are likely to miss H6N2 field infections. More concerning, sub-lineage I H6N2 viruses have acquired three of the nine HA mutations associated with human receptor-binding preference (A13S, V187D and A193N) since 2002. Most sub-lineage I viruses isolated since 2015 have acquired the K702R mutation in PB2 associated with the ability to infect humans, whereas prior to 2015 most viruses in sub-lineages I and II contained the avian lysine marker. All strains had an unusual HA0 motif of PQVETRGIF or PQVGTRGIF. Conclusions: The H6N2 viruses in South African chickens are mutating and reassorting amongst themselves but have remained a genetically pure lineage since they emerged more than 18 years ago. Greater efforts must be made by government and industry in the continuous isolation and characterization of field strains for use as HI antigens, new vaccine seed strains and to monitor the zoonotic threat of H6N2 viruses.

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Pathogenicity and transmission of a swine influenza A(H6N6) virus

Cited by 22 publications

References 53 publications

The Evolution, Spread and Global Threat of H6Nx Avian Influenza Viruses

The Evolution, Spread and Global Threat of H6Nx Avian Influenza Viruses

Tissue tropisms of avian influenza A viruses affect their spillovers from wild birds to pigs

Continuing evolution of H6N2 influenza A virus in South African chickens and the implications for diagnosis and control

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