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Virology. 2018 Apr 17;519:64-73. doi: 10.1016/j.virol.2018.04.004. [Epub ahead of print]
Three amino acid substitutions in the NS1 protein change the virus replication of H5N1 influenza virus in human cells.
Li J1, Zhang K2, Chen Q3, Zhang X3, Sun Y4, Bi Y4, Zhang S4, Gu J5, Li J5, Liu D6, Liu W7, Zhou J8.
Author information
Abstract
Influenza A viruses have sophisticated strategies to promote their own replication. Here, we found that three H5N1 influenza viruses display different replication patterns in human A549 and macrophage cells. The HN01 virus displayed poor replication compared to HN021 and JS01. In addition, the HN01 virus was unable to counteract the interferon response and block general gene expression. This capability was restored by three amino acid substitutions on the NS1 protein: K55E, K66E, and C133F, resulting in recovered binding to CPSF30 and decreased interferon response activity. Furthermore, a recombinant HN01 virus expressing either NS1-C133F or the triple mutation replicate with higher titers in human A549 cells and macrophages compared to the parent virus. These three amino acid mutations reveal a new pathway to alter H5N1 virus replication.
KEYWORDS:
H5N1 influenza virus; IFN response; NS1 protein; Virus replication
PMID: 29677653 DOI: 10.1016/j.virol.2018.04.004
Three amino acid substitutions in the NS1 protein change the virus replication of H5N1 influenza virus in human cells.
Li J1, Zhang K2, Chen Q3, Zhang X3, Sun Y4, Bi Y4, Zhang S4, Gu J5, Li J5, Liu D6, Liu W7, Zhou J8.
Author information
Abstract
Influenza A viruses have sophisticated strategies to promote their own replication. Here, we found that three H5N1 influenza viruses display different replication patterns in human A549 and macrophage cells. The HN01 virus displayed poor replication compared to HN021 and JS01. In addition, the HN01 virus was unable to counteract the interferon response and block general gene expression. This capability was restored by three amino acid substitutions on the NS1 protein: K55E, K66E, and C133F, resulting in recovered binding to CPSF30 and decreased interferon response activity. Furthermore, a recombinant HN01 virus expressing either NS1-C133F or the triple mutation replicate with higher titers in human A549 cells and macrophages compared to the parent virus. These three amino acid mutations reveal a new pathway to alter H5N1 virus replication.
KEYWORDS:
H5N1 influenza virus; IFN response; NS1 protein; Virus replication
PMID: 29677653 DOI: 10.1016/j.virol.2018.04.004