Dataset Information

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

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.

SUBMITTER: Itoh Y

PROVIDER: S-EPMC2748827 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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

Itoh Yasushi Y 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

Nature 20090801 7258

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 ...[more]

PMID: 19672242

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Project description:Human-to-swine transmission of seasonal influenza viruses has led to sustained human-like influenza viruses circulating in the U.S. swine population. While some reverse zoonotic-origin viruses adapt and become enzootic in swine, nascent reverse zoonoses may result in virus detections that are difficult to classify as "swine-origin" or "human-origin" due to the genetic similarity of circulating viruses. This is the case for human-origin influenza A(H1N1) pandemic 2009 (pdm09) viruses detected in pigs following numerous reverse zoonosis events since the 2009 pandemic. We report the identification of two human infections with A(H1N1)pdm09 viruses originating from swine hosts and classify them as "swine-origin" variant influenza viruses based on phylogenetic analysis and sequence comparison methods. Phylogenetic analyses of viral genomes from two cases revealed these viruses were reassortants containing A(H1N1)pdm09 hemagglutinin (HA) and neuraminidase (NA) genes with genetic combinations derived from the triple reassortant internal gene cassette. Follow-up investigations determined that one individual had direct exposure to swine in the week preceding illness onset, while another did not report swine exposure. The swine-origin A(H1N1) variant cases were resolved by full genome sequence comparison of the variant viruses to swine influenza genomes. However, if reassortment does not result in the acquisition of swine-associated genes and swine virus genomic sequences are not available from the exposure source, future cases may not be discernible. We have developed a pipeline that performs maximum likelihood analyses, a k-mer-based set difference algorithm, and random forest algorithms to identify swine-associated sequences in the hemagglutinin gene to differentiate between human-origin and swine-origin A(H1N1)pdm09 viruses.IMPORTANCE Influenza virus infects a wide range of hosts, resulting in illnesses that vary from asymptomatic cases to severe pneumonia and death. Viral transfer can occur between human and nonhuman hosts, resulting in human and nonhuman origin viruses circulating in novel hosts. In this work, we have identified the first case of a swine-origin influenza A(H1N1)pdm09 virus resulting in a human infection. This shows that these viruses not only circulate in swine hosts, but are continuing to evolve and distinguish themselves from previously circulating human-origin influenza viruses. The development of techniques for distinguishing human-origin and swine-origin viruses are necessary for the continued surveillance of influenza viruses. We show that unique genetic signatures can differentiate circulating swine-associated strains from circulating human-associated strains of influenza A(H1N1)pdm09, and these signatures can be used to enhance surveillance of swine-origin influenza.

Dataset Information

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

Publications

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

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