A Single-Amino-Acid Substitution in the NS1 Protein Changes the Pathogenicity of H5N1 Avian Influenza Viruses in Mice
Peirong Jiao,Guobin Tian,Yanbing Li,Guohua Deng,Yongping Jiang,Chang Liu,Weilong Liu,Zhigao Bu,Yoshihiro Kawaoka,Yoshihiro Kawaoka,Hualan Chen +10 more
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TLDR
It is demonstrated that the amino acid S42 of NS1 is critical for the H5N1 influenza virus to antagonize host cell interferon induction and for the NS1 protein to prevent the double-stranded RNA-mediated activation of the NF-κB pathway and the IRF-3 pathway.Abstract:
In this study, we explored the molecular basis determining the virulence of H5N1 avian influenza viruses in mammalian hosts by comparing two viruses, A/Duck/Guangxi/12/03 (DK/12) and A/Duck/Guangxi/27/03 (DK/27), which are genetically similar but differ in their pathogenicities in mice. To assess the genetic basis for this difference in virulence, we used reverse genetics to generate a series of reassortants and mutants of these two viruses. We found that a single-amino-acid substitution of serine for proline at position 42 (P42S) in the NS1 protein dramatically increased the virulence of the DK/12 virus in mice, whereas the substitution of proline for serine at the same position (S42P) completely attenuated the DK/27 virus. We further demonstrated that the amino acid S42 of NS1 is critical for the H5N1 influenza virus to antagonize host cell interferon induction and for the NS1 protein to prevent the double-stranded RNA-mediated activation of the NF-κB pathway and the IRF-3 pathway. Our results indicate that the NS1 protein is critical for the pathogenicity of H5N1 influenza viruses in mammalian hosts and that the amino acid S42 of NS1 plays a key role in undermining the antiviral immune response of the host cell.read more
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Emergence and pandemic potential of swine-origin H1N1 influenza virus.
TL;DR: Efforts to control these outbreaks and real-time monitoring of the evolution of this virus should provide invaluable information to direct infectious disease control programmes and to improve understanding of the factors that determine viral pathogenicity and/or transmissibility.
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The multifunctional NS1 protein of influenza A viruses.
TL;DR: The basic biochemistry of NS1 is summarized, in particular its synthesis, structure, and intracellular localization, and the various roles NS1 has in regulating viral replication mechanisms, host innate/adaptive immune responses, and cellular signalling pathways are discussed.
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Genetic analysis of novel avian A(H7N9) influenza viruses isolated from patients in China, February to April 2013.
Tsutomu Kageyama,Seiichiro Fujisaki,Emi Takashita,Hong Xu,Shinya Yamada,Yuko Uchida,Gabriele Neumann,Takehiko Saito,Takehiko Saito,Yoshihiro Kawaoka,Masato Tashiro +10 more
TL;DR: Several characteristic amino acid changes in HA and the PB2 RNA polymerase subunit probably facilitate binding to human-type receptors and efficient replication in mammals, respectively, highlighting the pandemic potential of the novel viruses.
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The pathogenesis of influenza virus infections: the contributions of virus and host factors
TL;DR: This work reviews the contributions of both virus and host factors to the pathogenesis of these viral infections and identifies several virulence factors in these virus strains.
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Genetics, Receptor Binding Property, and Transmissibility in Mammals of Naturally Isolated H9N2 Avian Influenza Viruses
Xuyong Li,Jianzhong Shi,Jing Guo,Guohua Deng,Qianyi Zhang,Jinliang Wang,Xijun He,Kaicheng Wang,Jiming Chen,Yuanyuan Li,Jun Fan,Huiui Kong,Chunyang Gu,Yuantao Guan,Yasuo Suzuki,Yoshihiro Kawaoka,Liling Liu,Yongping Jiang,Guobin Tian,Yanbing Li,Zhigao Bu,Hualan Chen +21 more
TL;DR: The study indicates that the widespread dissemination of H9N2 viruses poses a threat to human health not only because of the potential of these viruses to cause an influenza pandemic, but also because they can function as “vehicles” to deliver different subtypes of influenza viruses from avian species to humans.
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