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Pathogenicity of the H1N1 influenza virus enhanced by functional synergy between the NPV100I and NAD248N pair.
Kim, Woo-Jong; Hur, Kye-Yeon; Park, Han Wook; Lee, Seung-Woo; Yoo, Joo-Yeon.
Afiliación
  • Kim WJ; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
  • Hur KY; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
  • Park HW; Department of Integrative Biosciences & Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
  • Lee SW; Department of Integrative Biosciences & Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
  • Yoo JY; Organelle Network Research Center, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
PLoS One ; 14(5): e0217691, 2019.
Article en En | MEDLINE | ID: mdl-31150476
By comparing and measuring covariations of viral protein sequences from isolates of the 2009 pH1N1 influenza A virus (IAV), specific substitutions that co-occur in the NP-NA pair were identified. To investigate the effect of these co-occurring substitution pairs, the V100I substitution in NP and the D248N substitution in NA were introduced into laboratory-adapted WSN IAVs. The recombinant WSN with the covarying NPV100I-NAD248N pair exhibited enhanced pathogenicity, as characterized by increased viral production, increased death and inflammation of host cells, and high mortality in infected mice. Although direct interactions between the NPV100I and NAD248N proteins were not detected, the RNA-binding ability of NPV100I was increased, which was further strengthened by NAD248N, in expression-plasmid-transfected cells. Additionally, the NAD248N protein was frequently recruited within lipid rafts, indirectly affecting the RNA-binding ability of NP as well as viral release. Altogether, our data indicate that the covarying NPV100I-NAD248N pair obtained from 2009 pH1N1 IAV sequence information function together to synergistically augment viral assembly and release, which may explain the observed enhanced viral pathogenicity.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Proteínas Virales / Proteínas del Núcleo Viral / Gripe Humana / Subtipo H1N1 del Virus de la Influenza A Límite: Animals / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Proteínas Virales / Proteínas del Núcleo Viral / Gripe Humana / Subtipo H1N1 del Virus de la Influenza A Límite: Animals / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article