Receptor-binding specificity and transmissibility of H9 influenza viruses
Human infections with H9 influenza viruses have been infrequently reported (4, 137, 138), but epidemiological studies suggest that they may occur more frequently than currently recognized (reviewed in (139)). Viruses of the H9 subtype circulate widely in poultry and have also been isolated from pigs. Importantly, H9 viruses have donated genes to the currently circulating H5N1 (140-146) and H7N9 viruses (see ‘Sporadic Infections of Humans with Swine or Avian Influenza Viruses’). Many Asian H9N2 viruses have acquired the HA-Q226L mutation, which increases binding to human-type receptors (147, 148). Nonetheless, several avian H9N2 viruses tested did not transmit among ferrets via respiratory droplets, although two of these viruses infected co-housed, naïve animals (149). A reassortant possessing Asian H9N2 virus-derived HA (encoding HA-226L) and NA genes combined with the internal genes of a human H3N2 virus transmitted to ferret cage mates, but not via respiratory droplets to animals in adjacent cages (149). However, after ten sequential passages in ferrets, a virus was obtained that transmitted via respiratory droplets (150). Three amino acid changes in the surface glycoproteins (HA-T189A and -G510R, and NA-I28V) were responsible for this change in transmissibility (150). Based on this information, Kimble et al. (151) generated reassortants composed of 2009 pandemic H1N1 vRNA segments and the HA or HA/NA vRNA segments of the H9N2 ferret-transmissible virus, or the parent of the ferret-transmissible virus. Three of four reassortant viruses transmitted via respiratory droplets to naïve ferrets (151), further demonstrating the potential of avian/human reassortants to transmit among mammals via respiratory droplets.