The Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078, USA.
Viruses. 2023 Jun 22;15(7):1412. doi: 10.3390/v15071412.
Influenza A virus (IAV) is an eight-segment negative-sense RNA virus and is subjected to gene recombination between strains to form novel strains, which may lead to influenza pandemics. Seasonal influenza occurs annually and causes great losses in public healthcare. In this study, we examined the role of interferon-induced protein with tetratricopeptide repeats 1 and 2 (IFIT1 and IFIT2) in influenza virus infection. Knockdown of IFIT1 or IFIT2 using a lentiviral shRNA increased viral nucleoprotein (NP) and nonstructural protein 1 (NS1) protein levels, as well as progeny virus production in A/Puerto Rico/8/34 H1N1 (PR/8)-infected lung epithelial A549 cells. Overexpression of IFIT1 or IFIT2 reduced viral NP and NS1 RNA and protein levels in PR/8-infected HEK293 cells. Overexpression of IFIT1 or IFIT2 also inhibited influenza virus infection of various H1N1 strains, including PR/8, A/WSN/1933, A/California/07/2009 and A/Oklahoma/3052/2009, as determined by a viral reporter luciferase assay. Furthermore, knockdown of IFIT1 or IFIT2 increased while overexpression of IFIT1 or IFIT2 decreased viral RNA, complementary RNA, and mRNA levels of NP and NS1, as well as viral polymerase activities. Taken together, our results support that both IFIT1 and -2 have anti-influenza virus activities by inhibiting viral RNA synthesis.
甲型流感病毒（IAV）是一种具有八个节段的负义 RNA 病毒，易在不同株系间发生基因重组，从而形成新的病毒株，这可能导致流感大流行。季节性流感每年都会发生，给公共卫生保健带来巨大损失。在本研究中，我们研究了干扰素诱导的含有四肽重复结构域蛋白 1 和 2（IFIT1 和 IFIT2）在流感病毒感染中的作用。使用慢病毒 shRNA 敲低 IFIT1 或 IFIT2 会增加甲型流感病毒 A/Puerto Rico/8/34 H1N1（PR/8）感染的肺上皮 A549 细胞中的病毒核蛋白（NP）和非结构蛋白 1（NS1）蛋白水平以及子代病毒的产生。IFIT1 或 IFIT2 的过表达会降低 PR/8 感染的 HEK293 细胞中的病毒 NP 和 NS1 RNA 和蛋白水平。IFIT1 或 IFIT2 的过表达还抑制了各种 H1N1 株系（包括 PR/8、A/WSN/1933、A/California/07/2009 和 A/Oklahoma/3052/2009）的流感病毒感染，这通过病毒报告荧光素酶测定来确定。此外，IFIT1 或 IFIT2 的敲低会增加，而 IFIT1 或 IFIT2 的过表达会降低 NP 和 NS1 的病毒 RNA、互补 RNA 和 mRNA 水平以及病毒聚合酶活性。综上所述，我们的研究结果表明 IFIT1 和 IFIT2 均通过抑制病毒 RNA 合成具有抗流感病毒活性。
