Genetics, Receptor Binding Property, and Transmissibility in Mammals of Naturally Isolated H9N2 Avian Influenza Viruses

Abstract

H9N2 subtype influenza viruses have been detected in different species of wild birds and domestic poultry in many countries for several decades. Because these viruses are of low pathogenicity in poultry, their eradication is not a priority for animal disease control in many countries, which has allowed them to continue to evolve and spread. Here, we characterized the genetic variation, receptor-binding specificity, replication capability, and transmission in mammals of a series of H9N2 influenza viruses that were detected in live poultry markets in southern China between 2009 and 2013. Thirty-five viruses represented 17 genotypes on the basis of genomic diversity, and one specific “internal-gene-combination” predominated among the H9N2 viruses. This gene combination was also present in the H7N9 and H10N8 viruses that have infected humans in China. All of the 35 viruses preferentially bound to the human-like receptor, although two also retained the ability to bind to the avian-like receptor. Six of nine viruses tested were transmissible in ferrets by respiratory droplet; two were highly transmissible. Some H9N2 viruses readily acquired the 627K or 701N mutation in their PB2 gene upon infection of ferrets, further enhancing their virulence and transmission in mammals. Our study indicates that the widespread dissemination of H9N2 viruses poses a threat to human health not only because of the potential of these viruses to cause an influenza pandemic, but also because they can function as “vehicles” to deliver different subtypes of influenza viruses from avian species to humans.

Replication and transmission of mammalian-adapted H9 subtype influenza virus in pigs and quail

“…At least one of these isolates was transmitted with apparently higher efficiency, although the mean peak titres were lower than those observed for the H9N2 and H9N1 avian/human reassortants presented previously. The HA of the natural isolates from the study by Li et al (2014) have in common with our ferret-adapted P10 H9 the I155T mutation, which favours binding to a-2,6 sialic acid, which may favour replication in mammals. However, P10 HA also differed from the viruses described by Li et al…”

“…The animal origin of the H9N2 viruses (avian and swine) as well as different lineages (G1 and Y280) may account for these differences. A recent report from Li et al (2014) showed that some naturally occurring H9N2 isolates have the capacity for respiratory droplet transmission in ferrets without adaptation. At least one of these isolates was transmitted with apparently higher efficiency, although the mean peak titres were lower than those observed for the H9N2 and H9N1 avian/human reassortants presented previously.…”

“…It remains to be determined whether wholly avian H9N2 viruses from the Li et al (2014) study are compatible for replication and transmission in pigs. It also remains to be determined whether the viruses that showed improved replication and transmission in ferrets in the Li et al (2014) report will have a similar phenotype in pigs. Further detailed sequence analyses of viruses should shed light on the adaptive changes that take place during initial rounds of replication in different hosts.…”

“…In this regard, it is important to note that the ferret is widely used as an animal model to study airborne transmission of influenza viruses; adaptive changes that lead to such a phenotype have been identified in the H9, H7 and H5 subtypes (Herfst et al, 2012;Imai et al, 2013;Kimble et al, 2011;Ku et al, 2014;Li et al, 2014;Sorrell et al, 2009;Sutton et al, 2014;Wan et al, 2008). However, further studies are lacking to demonstrate whether the ferret-adaptive mutations increase or restrict the host range of the virus.…”

Prevalence, genetics, and transmissibility in ferrets of Eurasian avian-like H1N1 swine influenza viruses

“…We investigated the virulence in mice of the EAH1N1 SIVs as described previously (16). The 10 EAH1N1 SIVs replicated in the lungs of mice, nine SIVs were detected in the nasal turbinate of mice, and two were also detected in the kidneys (SI Appendix, Fig.…”