In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses

Influenza A viruses cause recurrent outbreaks of local or global scale with potentially severe consequences for human health and the global economy. Recently, a new strain of influenza A virus was detected that causes disease in and transmits among humans, probably owing to little or no pre-existing immunity to the new strain. On June 11, 2009, the WHO declared that the infections caused by the new strain had reached pandemic proportion. Characterized as an influenza A virus of the H1N1 subtype, the genomic segments of the new strain were most closely related to swine viruses1. Most human infections with swine-origin H1N1 influenza viruses (S-OIVs) appear to be mild; however, more than 50% of hospitalized individuals do not have underlying health issues, attesting to the pathogenic potential of S-OIVs. To better assess the risk posed by the new virus, we characterized one of the first US S-OIV isolates, A/California/04/09 (H1N1; CA04), as well as several other S-OIV isolates, in vitro and in vivo. In mice and ferrets, CA04 and other S-OIV isolates tested replicate more efficiently than a currently circulating human H1N1 virus. In addition, CA04 replicates efficiently in nonhuman primates, causes more severe pathologic lesions in the lungs of infected mice, ferrets, and nonhuman primates than a currently circulating human H1N1 virus, and transmits among ferrets. In specific-pathogen free miniature pigs, CA04 replicates without clinical symptoms. The assessment of human sera from different age groups suggests that infection with human H1N1 viruses antigenically closely related to viruses circulating in 1918 confers neutralizing antibody activity to CA04. Finally, we show that CA04 is sensitive to approved and experimental antiviral drugs, suggesting these compounds as a first line of defence against the recently declared S-OIV pandemic.