甲型流感病毒(IAVs)是一个主要的全球健康威胁,可能导致下一次大流行。尽管研究部分揭示了IAV与宿主相互作用的分子机制,这需要进一步的研究。在这项研究中,我们探讨了转运蛋白-3（TNPO3）在IAV感染中的作用。我们发现，TNPO3缺陷细胞抑制四种不同的IAV菌株的感染，而敲除（KO）细胞中TNPO3表达的恢复恢复了IAV感染。野生型(WT)细胞中的TNPO3过表达促进IAV感染,表明TNPO3参与IAV复制。此外，我们发现TNPO3的消耗抑制了IAV生命周期中的未涂层，从而抑制病毒核糖核蛋白（vRNP）进入细胞核的过程。然而,TNPO3的KO不影响病毒的附着，内吞作用,或内体酸化过程。随后，我们发现TNPO3可以与病毒蛋白M1和M2共定位并相互作用。一起来看,TNPO3的消耗抑制IAV脱膜，从而抑制IAV复制。我们的研究为揭示IAV复制机制和治疗流感疾病提供了新的见解和潜在的治疗靶点。
Influenza A viruses (IAVs) are a major global health threat and in the future, may cause the next pandemic. Although studies have partly uncovered the molecular mechanism of IAV-host interaction, it requires further research. In this study, we explored the roles of transportin-3 (
TNPO3) in IAV infection. We found that TNPO3-deficient cells inhibited infection with four different IAV strains, whereas restoration of
TNPO3 expression in knockout (KO) cells restored IAV infection.
TNPO3 overexpression in wild-type (WT) cells promoted IAV infection, suggesting that
TNPO3 is involved in the IAV replication. Furthermore, we found that TNPO3 depletion restrained the uncoating in the IAV life cycle, thereby inhibiting the process of viral ribonucleoprotein (vRNP) entry into the nucleus. However, KO of TNPO3 did not affect the virus attachment, endocytosis, or endosomal acidification processes. Subsequently, we found that
TNPO3 can colocalize and interact with viral proteins M1 and M2. Taken together, the depletion of
TNPO3 inhibits IAV uncoating, thereby inhibiting IAV replication. Our study provides new insights and potential therapeutic targets for unraveling the mechanism of IAV replication and treating influenza disease.
