. "A5 In Vitro and In Vivo Characterization of New Swine-Origin H1N1 Influenza Viruses." The Domestic and International Impacts of the 2009-H1N1 Influenza A Pandemic: Global Challenges, Global Solutions: Workshop Summary. Washington, DC: The National Academies Press, 2010.
The following HTML text is provided to enhance online
readability. Many aspects of typography translate only awkwardly to HTML.
Please use the page image
as the authoritative form to ensure accuracy.
The Domestic and International Impacts of the 2009-H1N1 Influenza a Pandemic: Global Challenges, Global Solutions - Workshop Summary
Influenza A viruses cause recurrent outbreaks at local or global scalewith potentially severe consequences for human health and the global economy. Recently, a new strain of influenza A virus was detected that causesdisease in and transmits among humans, probably owing to little or nopre-existing immunity to the new strain. On 11 June 2009 the World HealthOrganization declared that the infections caused by the new strain hadreached pandemic proportion. Characterized as an influenza A virus of theH1N1 subtype, the genomic segments of the new strain were most closelyrelated to swine viruses (Novel Swine-Origin Influenza A [H1N1] VirusInvestigation Team, 2009). Most human infections with swine origin H1N1influenza viruses (S-OIVs) seem to be mild; however, a substantial numberof hospitalized individuals do not have underlying health issues, attestingto the pathogenic potential of S-OIVs. To achieve a better assessment ofthe risk posed by the new virus, we characterized one of the first US S-OIVisolates, A/California/04/09 (H1N1; hereafter referred to as CA04), as well asseveral other S-OIV isolates, in vitro and in vivo. In mice and ferrets, CA04and other S-OIV isolates tested replicate more efficiently than a currentlycirculating human H1N1 virus. In addition, CA04 replicates efficiently innon-human primates, causes more severe pathological lesions in the lungs ofinfected mice, ferrets and non-human primates than a currently circulatinghuman H1N1 virus, and transmits among ferrets. In specific-pathogen-freeminiature pigs, CA04 replicates without clinical symptoms. The assessmentof human sera from different age groups suggests that infection with humanH1N1 viruses antigenically closely related to viruses circulating in 1918confers neutralizing antibody activity to CA04. Finally, we show that CA04is sensitive to approved and experimental antiviral drugs, suggesting thatthese compounds could function as a first line of defence against the recentlydeclared S-OIV pandemic.
Sequence analyses of recently emerged swine-origin H1N1 viruses (S-OIVs) revealed the absence of markers associated with high pathogenicity in avian and/or mammalian species, such as a multibasic haemagglutinin (HA) cleavage site (Kawaoka and Webster, 1988) or lysine at position 627 of the PB2 protein (Hatta et al., 2001). To characterize the new viruses in vitro and in vivo, we amplified the following S-OIVs in Madin–Darby canine kidney (MDCK) cells: A/California/04/09 (CA04), A/Wisconsin/WSLH049/09 (WSLH049), A/Wisconsin/WSLH34939/09 (WSLH34939), A/Netherlands/603/09 (Net603) and A/Osaka/164/09 (Osaka164). WSLH34939 was isolated from a patient who required hospitalization, whereas the remaining viruses were isolated from mild cases. These viruses represent the currently recognized neuraminidase (NA) variants among S-OIVs: CA04, NA-106V, NA-248N; Osaka164, NA-106I, NA-248N; WSLH049, NA-106I, NA-248D; WSLH34939, NA-106I, NA-248D; and Net603, NA-106V, NA-248N.