H1N1/H5N1


Increased pathogenicity of a reassortant 2009 pandemic H1N1 influenza virus containing an H5N1 hemagglutinin


A novel H1N1 influenza virus emerged in 2009 (pH1N1) to become the first influenza pandemic of the 21st century. This virus is now co-circulating with highly pathogenic H5N1 avian influenza viruses in many parts of the world, raising concerns that a reassortment event may lead to highly pathogenic influenza strains with the capacity to infect humans more readily and cause severe disease. To investigate the virulence of pH1N1-H5N1 reassortant viruses we created pH1N1 (A/California/04/2009) viruses expressing individual genes from an avian H5N1 influenza strain (A/Hong Kong/483/1997). Using several in vitro models of virus replication, we observed increased replication for a reassortant CA/09 virus expressing the hemagglutinin (HA) gene of HK/483 (CA/09-483HA) relative to either parental CA/09 virus or reassortant CA/09 expressing other HK/483 genes. This increased replication correlated with enhanced pathogenicity in infected mice similar to the parental HK/483 strain. Serial passage of the CA/09 parental virus and the CA/09-483HA virus through primary human lung epithelial cells resulted in increased pathogenicity, suggesting that these viruses may easily adapt to humans and become more virulent. In contrast, serial passage attenuated the parental HK/483 virus in vitro, and resulted in slightly reduced morbidity in vivo, suggesting that sustained replication in humans may attenuate H5N1 avian influenza viruses. Together, these data suggest that reassortment between co-circulating human pH1N1 and avian H5N1 influenza strains may result in a virus with the potential for increased pathogenicity in mammals.

http://jvi.asm.org/cgi/content/short/JVI.05582-11v1