Transportin-3 Facilitates Uncoating of Influenza A Virus

Abstract

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.

GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor binding

“…Individual sgRNA constructs targeting GGCX were generated and incorporated into the lenti-sgRNA-EGFP vector. Lentiviruses were produced following established protocols 43 . These lentiviruses were then transduced into PK-15-Cas9 cells.…”

“…To examine the impact of GGCX-KO on cellular proliferation, the viability of GGCX-KO cells and WT cells was measured through CCK-8 activity, following the manufacturer's instructions 43 . Briefly, cells were seeded onto 96-well plates, and their viabilities were measured at 12-, 24-, and 36-hours post-seeding.…”