Influenza A viruses cause recurrent outbreaks at 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 11 June 2009 the World Health Organization 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) seem to be mild; however, a substantial number of hospitalized individuals do not have underlying health issues, attesting to the pathogenic potential of S-OIVs. To achieve a better assessment of the risk posed by the new virus, we characterized one of the first US S-OIV isolates, A/California/04/09 (H1N1; hereafter referred to as 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 non-human primates, causes more severe pathological lesions in the lungs of infected mice, ferrets and non-human 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 that these compounds could function as a first line of defence against the recently declared S-OIV pandemic.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
We thank the Centers for Disease Control (CDC) for A/California/04/09 virus and R. Fouchier for A/Netherlands/603/09 virus. We thank K. Wells for editing the manuscript, and M. McGregor, R. Moritz, A. Hanson, H. Ishida, H. Tsuchiya, R. Torii, N. Yamamoto, K. Soda, N. Nomura and H. Yoshida for technical assistance. We also thank T. Umemura, Y. Sunden and T. Tanaka for pathological analyses of virus-infected pigs. This work was supported by National Institute of Allergy and Infectious Diseases Public Health Service research grants, by an NIAID-funded Center for Research on Influenza Pathogenesis (CRIP, HHSN266200700010C), by Grant-in-Aid for Specially Promoted Research, by a contract research fund for the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases from the Ministry of Education, Culture, Sports, Science and Technology, and by grants-in-aid from the Ministry of Health and by ERATO (Japan Science and Technology Agency).
Author Contributions Y.I., K.S., M.K., T.W., Y.S., M.H., Y.M., D.T., Y.S.-T., T.N., M. Imai, S.W., K.I.-H., T.H., N.S., H.K., K.O. and Y.K. designed the experiments; Y.I., K.S., M.K., T.W., Y.S., M.H., D.T., Y.S.-T., T.N., S.S., M. Imai, Y.H., S.W., C.L., S.Y., K.F., S.M., H. Imai, S.K., M. Ito, R.T., K.I.-H., M.S., T.H., Kei Takahashi, A.M., H. Ishigaki, M. Nakayama, M. Okamatsu, Kazuo Takahashi, D.W., P.A.S., R.S., H.S., Y.F., M. Yamashita, K.M., K.N., M. Nakamura, R.B.-S., J.G., H.M. and M. Yamazaki performed the experiments; Y.I., K.S., M.K., T.W., Y.S., M.H., Y.M., Y.S.-T., T.N., M. Imai, S.W., C.L., S.Y., K.I.-H., T.H., H.G., M.S., M. Ozawa, G.N., H.K., K.O. and Y.K. analysed data; Y.I., K.S., M.K., T.W., Y.S., M.H., Y.M., Y.S.-T., T.N., M. Imai, K.I.-H., M.S., M. Ozawa, G.N., K.O. and Y.K. wrote the manuscript. Y.I., K.S., M.K., T.W., Y.S., M.H. and Y.M. contributed equally to this work.
This file contains Supplementary Table 9 which consists of a serum donor list.