In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses.
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 viruses. 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.
Itoh
Yasushi
Y
Department of Pathology, Shiga University of Medical Science, Ohtsu, Shiga 520-2192, Japan.
Shinya
Kyoko
K
Kiso
Maki
M
Watanabe
Tokiko
T
Sakoda
Yoshihiro
Y
Hatta
Masato
M
Muramoto
Yukiko
Y
Tamura
Daisuke
D
Sakai-Tagawa
Yuko
Y
Noda
Takeshi
T
Sakabe
Saori
S
Imai
Masaki
M
Hatta
Yasuko
Y
Watanabe
Shinji
S
Li
Chengjun
C
Yamada
Shinya
S
Fujii
Ken
K
Murakami
Shin
S
Imai
Hirotaka
H
Kakugawa
Satoshi
S
Ito
Mutsumi
M
Takano
Ryo
R
Iwatsuki-Horimoto
Kiyoko
K
Shimojima
Masayuki
M
Horimoto
Taisuke
T
Goto
Hideo
H
Takahashi
Kei
K
Makino
Akiko
A
Ishigaki
Hirohito
H
Nakayama
Misako
M
Okamatsu
Masatoshi
M
Takahashi
Kazuo
K
Warshauer
David
D
Shult
Peter A
PA
Saito
Reiko
R
Suzuki
Hiroshi
H
Furuta
Yousuke
Y
Yamashita
Makoto
M
Mitamura
Keiko
K
Nakano
Kunio
K
Nakamura
Morio
M
Brockman-Schneider
Rebecca
R
Mitamura
Hiroshi
H
Yamazaki
Masahiko
M
Sugaya
Norio
N
Suresh
M
M
Ozawa
Makoto
M
Neumann
Gabriele
G
Gern
James
J
Kida
Hiroshi
H
Ogasawara
Kazumasa
K
Kawaoka
Yoshihiro
Y
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D005260:Female; D005289:Ferrets / Q000821:virology; D015707:HN Protein / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000201:enzymology / Q000472:pathogenicity / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008252:Macaca fascicularis / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000635:transmission / Q000821:virology; D018419:Primate Diseases / Q000473:pathology / Q000821:virology; D013552:Swine / Q000821:virology*; D013553:Swine Diseases / Q000473:pathology / Q000821:virology; D013556:Swine, Miniature / Q000821:virology; D014779:Virus Replication
D000914:Antibodies, Viral; D000998:Antiviral Agents; D015707:HN Protein