MOE Joint International Research Laboratory of Animal Immunology, Nanjing Agricultural University, Nanjing, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, VA, USA.
Virology. 2018 Jun;519:64-73. doi: 10.1016/j.virol.2018.04.004. Epub 2018 Apr 17.
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.
甲型流感病毒具有复杂的策略来促进自身复制。在这里，我们发现三种 H5N1 流感病毒在人 A549 和巨噬细胞中的复制模式不同。与 HN021 和 JS01 相比，HN01 病毒的复制能力较差。此外，HN01 病毒无法抵抗干扰素反应并阻断一般基因表达。NS1 蛋白上的三个氨基酸取代（K55E、K66E 和 C133F）恢复了这种能力，导致与 CPSF30 的结合恢复和干扰素反应活性降低。此外，表达 NS1-C133F 或三重突变的重组 HN01 病毒在人 A549 细胞和巨噬细胞中的复制滴度比亲本病毒高。这三个氨基酸突变揭示了改变 H5N1 病毒复制的新途径。
