Avian-Type Receptor-Binding Ability Can Increase Influenza Virus Pathogenicity in Macaques

作者：Watanabe Tokiko^*; Shinya Kyoko; Watanabe Shinji; Imai Masaki; Hatta Masato; Li Chengjun; Wolter Ben F; Neumann Gabriele; Hanson Anthony; Ozawa Makoto; Yamada Shinya; Imai Hirotaka; Sakabe Saori; Takano Ryo; Iwatsuki Horimoto Kiyoko; Kiso Maki; Ito Mutsumi; Fukuyama Satoshi; Kawakami Eiryo; Gorai Takeo; Simmons Heather A; Schenkman Daniel; Brunner Kevin; Capuano Saverio V III; Weinfurter Jason T; Nishio Wataru; Maniwa Yoshimasa; Igarashi Tatsuhiko; Makino Akiko

来源：Journal of Virology, 2011, 85(24): 13195-13203.

DOI：10.1128/JVI.00859-11

The first influenza pandemic of the 21st century was caused by novel H1N1 viruses that emerged in early 2009. An Asp-to-Gly change at position 222 of the receptor-binding protein hemagglutinin (HA) correlates with more-severe infections in humans. The amino acid at position 222 of HA contributes to receptor-binding specificity with Asp (typically found in human influenza viruses) and Gly (typically found in avian and classic H1N1 swine influenza viruses), conferring binding to human-and avian-type receptors, respectively. Here, we asked whether binding to avian-type receptors enhances influenza virus pathogenicity. We tested two 2009 pandemic H1N1 viruses possessing HA-222G (isolated from severe cases) and two viruses that possessed HA-222D. In glycan arrays, viruses possessing HA-222D preferentially bound to human-type receptors, while those encoding HA-222G bound to both avian-and human-type receptors. This difference in receptor binding correlated with efficient infection of viruses possessing HA-222G, compared to those possessing HA-222D, in human lung tissue, including alveolar type II pneumocytes, which express avian-type receptors. In a nonhuman primate model, infection with one of the viruses possessing HA-222G caused lung damage more severe than did infection with a virus encoding HA-222D, although these pathological differences were not observed for the other virus pair with either HA-222G or HA-222D. These data demonstrate that the acquisition of avian-type receptor-binding specificity may result in more-efficient infection of human alveolar type II pneumocytes and thus more-severe lung damage. Collectively, these findings suggest a new mechanism by which influenza viruses may become more pathogenic in mammals, including humans.

• 出版日期2011-12
• 单位河北医科大学