Tweet
J Virol. 2017 Aug 16. pii: JVI.00637-17. doi: 10.1128/JVI.00637-17. [Epub ahead of print]
Zoonotic Risk, Pathogenesis, and Transmission of Avian-Origin H3N2 Canine Influenza Virus.
Sun H1, Blackmon S1, Yang G1, Waters K1, Li T2, Tangwangvivat R1, Xu Y1, Shyu D1, Wen F1, Cooley J3, Senter L4, Lin X2, Jarman R2, Hanson L1, Webby R5, Wan XF6.
Author information
Abstract
Two subtypes of influenza A virus (IAV), avian-origin canine influenza virus H3N2 (CIV-H3N2) and equine-origin CIV-H3N8, are enzootic in the canine population. Dogs have demonstrated seroconversion to diverse IAVs and naturally occurring reassortants of CIV-H3N2 and the 2009 H1N1 pandemic virus (pdmH1N1) have been isolated. We conducted a thorough phenotypic evaluation of CIV-H3N2 in order to assess its threat to human health. Using ferret-generated antisera we determined that CIV-H3N2 is antigenically distinct from contemporary human H3N2 IAVs, suggesting there may be minimal herd immunity in humans. We assessed the public health risk of CIV-H3N2?pdmH1N1 reassortants by characterizing in vitro genetic compatibility and in vivo pathogenicity and transmissibility. Using a luciferase minigenome assay, we quantified the polymerase activity of all possible 16 ribonucleoprotein (RNP) complexes (PB2, PB1, PA, NP) between CIV-H3N2 and pdmH1N1 identifying some combinations that were more active than either parental virus complex. Using reverse genetics, and fixing the CIV-H3N2 HA, we found that 51 of the 127 possible reassortant viruses were viable and able to be rescued. Nineteen of these reassortant viruses had high in vitro growth phenotypes and 13 of these replicated in mice lungs. A single reassortant with the NP and HA gene segments from CIV-H3N2 was selected for characterization in ferrets. The reassortant efficiently transmitted by contact but not airborne routes and was pathogenic in ferrets. Our results suggest that CIV-H3N2 reassortants may pose a moderate risk to public health and that the canine host should be monitored for emerging IAVs.Importance IAV pandemics are caused by the introduction of novel viruses that are capable of efficient and sustained human transmission into a human population with limited herd immunity. The dog, as a potential "mixing vessel" for avian and mammalian IAVs, represents a human health concern due to their susceptibility to infection, large global population and close physical contact with humans. Our results suggest that humans are likely to have limited preexisting immunity to CIV-H3N2 and that CIV-H3N2?pdmH1N1 reassortants have moderate genetic compatibility and are transmissible by direct contact in ferrets. Our study contributes to the increasing evidence that IAV surveillance in the canine population is an important component of pandemic preparedness.
Copyright ? 2017 American Society for Microbiology.
PMID: 28814512 DOI: 10.1128/JVI.00637-17
Zoonotic Risk, Pathogenesis, and Transmission of Avian-Origin H3N2 Canine Influenza Virus.
Sun H1, Blackmon S1, Yang G1, Waters K1, Li T2, Tangwangvivat R1, Xu Y1, Shyu D1, Wen F1, Cooley J3, Senter L4, Lin X2, Jarman R2, Hanson L1, Webby R5, Wan XF6.
Author information
Abstract
Two subtypes of influenza A virus (IAV), avian-origin canine influenza virus H3N2 (CIV-H3N2) and equine-origin CIV-H3N8, are enzootic in the canine population. Dogs have demonstrated seroconversion to diverse IAVs and naturally occurring reassortants of CIV-H3N2 and the 2009 H1N1 pandemic virus (pdmH1N1) have been isolated. We conducted a thorough phenotypic evaluation of CIV-H3N2 in order to assess its threat to human health. Using ferret-generated antisera we determined that CIV-H3N2 is antigenically distinct from contemporary human H3N2 IAVs, suggesting there may be minimal herd immunity in humans. We assessed the public health risk of CIV-H3N2?pdmH1N1 reassortants by characterizing in vitro genetic compatibility and in vivo pathogenicity and transmissibility. Using a luciferase minigenome assay, we quantified the polymerase activity of all possible 16 ribonucleoprotein (RNP) complexes (PB2, PB1, PA, NP) between CIV-H3N2 and pdmH1N1 identifying some combinations that were more active than either parental virus complex. Using reverse genetics, and fixing the CIV-H3N2 HA, we found that 51 of the 127 possible reassortant viruses were viable and able to be rescued. Nineteen of these reassortant viruses had high in vitro growth phenotypes and 13 of these replicated in mice lungs. A single reassortant with the NP and HA gene segments from CIV-H3N2 was selected for characterization in ferrets. The reassortant efficiently transmitted by contact but not airborne routes and was pathogenic in ferrets. Our results suggest that CIV-H3N2 reassortants may pose a moderate risk to public health and that the canine host should be monitored for emerging IAVs.Importance IAV pandemics are caused by the introduction of novel viruses that are capable of efficient and sustained human transmission into a human population with limited herd immunity. The dog, as a potential "mixing vessel" for avian and mammalian IAVs, represents a human health concern due to their susceptibility to infection, large global population and close physical contact with humans. Our results suggest that humans are likely to have limited preexisting immunity to CIV-H3N2 and that CIV-H3N2?pdmH1N1 reassortants have moderate genetic compatibility and are transmissible by direct contact in ferrets. Our study contributes to the increasing evidence that IAV surveillance in the canine population is an important component of pandemic preparedness.
Copyright ? 2017 American Society for Microbiology.
PMID: 28814512 DOI: 10.1128/JVI.00637-17