Bibliographic Details
| Title: |
PB2 residue 473 contributes to the mammalian virulence of H7N9 avian influenza virus by modulating viral polymerase activity via ANP32A. |
| Authors: |
Miaomiao Zhang1,2, Mingbin Liu1, Hongjun Chen2, Tianyi Qiu3, Xuanxuan Jin4, Weihui Fu1, Qiaoyang Teng2, Chen Zhao1 chen_zhao72@163.com, Jianqing Xu1,3 xujianqing@fudan.edu.cn, Zejun Li2 lizejun@shvri.ac.cn, Xiaoyan Zhang1,3 zhangxiaoyan@fudan.edu.cn |
| Source: |
Journal of Virology. Mar2024, Vol. 98 Issue 3, p1-19. 19p. |
| Subject Terms: |
*INFLUENZA A virus, H7N9 subtype, *VIRUS virulence, *POLYMERASES |
| Abstract: |
Since the first human infection reported in 2013, H7N9 avian influenza virus (AIV) has been regarded as a serious threat to human health. In this study, we sought to identify the virulence determinant of the H7N9 virus in mammalian hosts. By comparing the virulence of the SH/4664 H7N9 virus, a non-virulent H9N2 virus, and various H7N9-H9N2 hybrid viruses in infected mice, we first pinpointed PB2 as the primary viral factor accounting for the difference between H7N9 and H9N2 in mammalian virulence. We further analyzed the in vivo effects of individually mutating H7N9 PB2 residues different from the closely related H9N2 virus and consequently found residue 473, alongside the well-known residue 627, to be critical for the virulence of the H7N9 virus in mice and the activity of its reconstituted viral polymerase in mammalian cells. The importance of PB2-473 was further strengthened by studying reverse H7N9 substitutions in the H9N2 background. Finally, we surprisingly found that species-specific usage of ANP32A, a family member of host factors connecting with the PB2-627 polymorphism, mediates the contribution of PB2 473 residue to the mammalian adaption of AIV polymerase, as the attenuating effect of PB2 M473T on the viral polymerase activity and viral growth of the H7N9 virus could be efficiently complemented by co-expression of chicken ANP32A but not mouse ANP32A and ANP32B. Together, our studies uncovered the PB2 473 residue as a novel viral host range determinant of AIVs via s pecies-specific co-opting of the ANP32 host factor to support viral polymerase activity. [ABSTRACT FROM AUTHOR] |
|
Copyright of Journal of Virology is the property of American Society for Microbiology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Academic Search Complete |
