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Ryuta Uraki,
Maki Kiso,
Kyoko Shinya,
Hideo Goto,
Ryo Takano,
Kiyoko Iwatsuki-Horimoto, Kazuo Takahashi,
Rod S Daniels,
Olav Hungnes,
Tokiko Watanabe,
Yoshihiro Kawaoka
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ABSTRACT: A novel swine-origin H1N1 influenza virus [A(H1N1)pdm09 virus] caused the 2009 influenza pandemic. Most patients exhibited mild symptoms similar to seasonal influenza, but some experienced severe clinical signs and, in the worst cases, died. Such differences in symptoms are generally associated with preexisting medical conditions, but recent reports indicate the possible involvement of viral factors in clinical severity. To better understand the mechanism of pathogenicity of the A(H1N1)pdm09 virus, here, we compared five viruses that are genetically similar but were isolated from patients with either severe or mild symptoms. In a mouse model, Norway3487 virus exhibited greater pathogenicity than did Osaka164 virus. By exploiting reassortant viruses between these two viruses, we found that viruses possessing the HA gene of Norway3487 in the genetic background of Osaka164 were more pathogenic in mice compared with other reassortant viruses, indicating a role for HA in the high virulence of Norway3487 virus. Intriguingly, a virus possessing HA, NA, and NS derived from Norway3487 exhibited greater pathogenicity in mice in concert with PB2 and PB1 derived from Osaka164 than did the parental Norway3487 virus. These findings demonstrate that reassortment between A(H1N1)pdm09 viruses can lead to increased pathogenicity and highlight the need for continued surveillance of A(H1N1)pdm09 viruses.
Journal of Virology 12/2012; · 5.40 Impact Factor
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Kiyoko Iwatsuki-Horimoto,
Taisuke Horimoto,
Daisuke Tamura,
Maki Kiso,
Eiryo Kawakami,
Shuji Hatakeyama,
Yasuhiro Ebihara,
Tomohiko Koibuchi,
Takeshi Fujii, Kazuo Takahashi, [......],
Yuko Sakai-Tagawa,
Mutsumi Ito,
Saori Sakabe,
Ayaka Iwasa,
Kei Takahashi,
Takashi Ishii,
Takeo Gorai,
Koichiro Tsuji,
Aikichi Iwamoto,
Yoshihiro Kawaoka
[show abstract]
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ABSTRACT: Since its emergence, the 2009 pandemic H1N1 virus has spread rapidly throughout the world. Previously, we reported that most individuals born after 1920 do not have cross-reactive virus-neutralizing antibodies against pandemic (H1N1) 2009 virus, indicating that they were immunologically naïve to the pandemic virus prior to its emergence. This finding provided us with an excellent opportunity for a seroepidemiological investigation of the transmission mode of the pandemic virus in the community. To gain insight into its transmission within communities, we performed a serosurvey for pandemic virus infection with schoolchildren at an elementary school in Tokyo, Japan, and their parents. We observed a high prevalence of neutralizing antibodies to the pandemic virus in the children at this school, although the percentage of children positive for the neutralizing antibodies varied among classrooms. While a much lower prevalence was observed among parents, seropositivity of the parents correlated with that of their schoolchildren. Moreover, many adults appeared to have experienced asymptomatic infection with the pandemic virus. These data suggest that the pandemic virus was readily transmitted among schoolchildren in elementary schools and that it was also transmitted from schoolchildren to their parents.
Clinical and vaccine immunology: CVI 02/2011; 18(5):860-6. · 2.37 Impact Factor
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Jean-Étienne Morlighem,
Shintaro Aoki,
Mami Kishima,
Mitsue Hanami,
Chihiro Ogawa,
Amadu Jalloh,
Yukari Takahashi,
Yuki Kawai,
Satomi Saga,
Eiji Hayashi, [......],
Yukihiro Koretsune,
Koichiro Kudo,
Yuji Himeno,
Aizan Hirai, Kazuo Takahashi,
Yuko Sakai-Tagawa,
Kiyoko Iwatsuki-Horimoto,
Yoshihiro Kawaoka,
Yoshihide Hayashizaki,
Toshihisa Ishikawa
[show abstract]
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ABSTRACT: Pandemic influenza A(H1N1) virus infection quickly circulated worldwide in 2009. In Japan, the first case was reported in May 2009, one month after its outbreak in Mexico. Thereafter, A(H1N1) infection spread widely throughout the country. It is of great importance to profile and understand the situation regarding viral mutations and their circulation in Japan to accumulate a knowledge base and to prepare clinical response platforms before a second pandemic (pdm) wave emerges.
A total of 253 swab samples were collected from patients with influenza-like illness in the Osaka, Tokyo, and Chiba areas both in May 2009 and between October 2009 and January 2010. We analyzed partial sequences of the hemagglutinin (HA) and neuraminidase (NA) genes of the 2009 pdm influenza virus in the collected clinical samples. By phylogenetic analysis, we identified major variants of the 2009 pdm influenza virus and critical mutations associated with severe cases, including drug-resistance mutations.
Our sequence analysis has revealed that both HA-S220T and NA-N248D are major non-synonymous mutations that clearly discriminate the 2009 pdm influenza viruses identified in the very early phase (May 2009) from those found in the peak phase (October 2009 to January 2010) in Japan. By phylogenetic analysis, we found 14 micro-clades within the viruses collected during the peak phase. Among them, 12 were new micro-clades, while two were previously reported. Oseltamivir resistance-related mutations, i.e., NA-H275Y and NA-N295S, were also detected in sporadic cases in Osaka and Tokyo.
PLoS ONE 01/2011; 6(4):e18956. · 4.09 Impact Factor
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Yasushi Itoh,
Kyoko Shinya,
Maki Kiso,
Tokiko Watanabe,
Yoshihiro Sakoda,
Masato Hatta,
Yukiko Muramoto,
Daisuke Tamura,
Yuko Sakai-Tagawa,
Takeshi Noda, [......],
Hiroshi Mitamura,
Masahiko Yamazaki,
Norio Sugaya,
M Suresh,
Makoto Ozawa,
Gabriele Neumann,
James Gern,
Hiroshi Kida,
Kazumasa Ogasawara,
Yoshihiro Kawaoka
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ABSTRACT: 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.
Nature 08/2009; 460(7258):1021-5. · 36.28 Impact Factor
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Yasushi Itoh,
Kyoko Shinya,
Maki Kiso,
Tokiko Watanabe,
Yoshihiro Sakoda,
Masato Hatta,
Yukiko Muramoto,
Daisuke Tamura,
Yuko Sakai-Tagawa,
Takeshi Noda, [......],
Hiroshi Mitamura,
Masahiko Yamazaki,
Norio Sugaya,
M. Suresh,
Makoto Ozawa,
Gabriele Neumann,
James Gern,
Hiroshi Kida,
Kazumasa Ogasawara,
Yoshihiro Kawaoka
[show abstract]
[hide abstract]
ABSTRACT: 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
Nature 07/2009; 460(7258):1021-1025. · 36.28 Impact Factor
