Origins and Evolutionary Dynamics of H3N2 Canine Influenza Virus

Abstract

Influenza A viruses (IAVs) are maintained mainly in wild birds, and despite frequent spillover infections of avian IAVs into mammals, only a small number of viruses have become established in mammalian hosts. A new H3N2 canine influenza virus (CIV) of avian origin emerged in Asia in the mid-2000s and is now circulating in dog populations of China and South Korea, and possibly in Thailand. The emergence of CIV provides new opportunities for zoonotic infections and interspecies transmission. We examined 14,764 complete IAV genomes together with all CIV genomes publicly available since its first isolation until 2013. We show that CIV may have originated as early as 1999 as a result of segment reassortment among Eurasian and North American avian IAV lineages. We also identified amino acid changes that might have played a role in CIV emergence, some of which have not been previously identified in other cross-species jumps. CIV evolves at a lower rate than H3N2 human influenza viruses do, and viral phylogenies exhibit geographical structure compatible with high levels of local transmission. We detected multiple intrasubtypic and heterosubtypic reassortment events, including the acquisition of the NS segment of an H5N1 avian influenza virus that had previously been overlooked. In sum, our results provide insight into the adaptive changes required by avian viruses to establish themselves in mammals and also highlight the potential role of dogs to act as intermediate hosts in which viruses with zoonotic and/or pandemic potential could originate, particularly with an estimated dog population of ϳ700 million. IMPORTANCEInfluenza A viruses circulate in humans and animals. This multihost ecology has important implications, as past pandemics were caused by IAVs carrying gene segments of both human and animal origin. Adaptive evolution is central to cross-species jumps, and this is why understanding the evolutionary processes that shape influenza A virus genomes is key to elucidating the mechanisms underpinning viral emergence. An avian-origin canine influenza virus (CIV) has recently emerged in dogs and is spreading in Asia. We reconstructed the evolutionary history of CIV and show that it originated from both Eurasian and North American avian lineages. We also identified the mutations that might have been responsible for the cross-species jump. Finally, we provide evidence of multiple reassortment events between CIV and other influenza viruses (including an H5N1 avian virus). This is a cause for concern, as there is a large global dog population to which humans are highly exposed.

Assessment of Molecular, Antigenic, and Pathological Features of Canine Influenza A(H3N2) Viruses That Emerged in the United States

“…Similar to viruses detected in eastern Asia, the US CIVs had a Leu at position 222, differentiating them from avian H3 IAVs, which typically have a highly conserved Trp at this position. Interestingly, Leu at position 222 was also shared among A(H3N8) CIVs circulating in the United States, suggesting its potential role in adaptation of these viruses to dogs [26–28]. Glycan-binding analyses of recombinant CIV HA revealed a strong binding preference for the α2–3-linked SAs and mixed α2–3/α2–6 branched SAs (numbers 65 and 66).…”

“…Evidence indicating that dogs can be infected with both canine and human influenza viruses raises the concern that a reassortant virus could emerge that is capable of infecting humans. The emergence of this new A(H3N2) CIV and the continued antigenic drift and reassortment [28] that it demonstrates in mammals warrants global surveillance and a better understanding of the pathogenesis and the potential for transmission of these viruses. Risk assessments such as these will improve our pandemic preparedness and will help mitigate the risk of zoonotic influenza virus infections and the threat to public health.…”

Origin, Genetic Diversity, and Evolutionary Dynamics of Novel Porcine Circovirus 3

“…A Bayesian skyline coalescent model was set to estimate the efficient population size. Two independent runs were operated with a chain length of 1 × 10 8 generations and sampled at every 10 000 generations 57. Convergence was estimated based on the software Tracer (v1.6) (http://tree.bio.ed.ac.uk/software/tracer/) after a burn‐in of 10%.…”

Emergence and adaptation of H3N2 canine influenza virus from avian influenza virus: An overlooked role of dogs in interspecies transmission

“…H3N2 FIV isolates were included in the data set for the origin and genotyping analysis. Although H3N2 FIV has been isolated in cats, it is essentially H3N2 CIV (Park et al., ; Zhu et al., ).…”