Abstract Title
Role of host factors in the fusion and nuclear import of vRNP complex of influenza virus
Abstract
Influenza A virus (IAV) commandeers numerous host cellular factors for successful replication. Recently, we identified mannose-6-phosphate receptor (M6PR) as a novel host factor for the efficient replication of IAV and demonstrated its involvement in the fusion of viral and late endosomal membranes. Mechanistically, the lumenal domain of M6PR interacted with the residues 17-127 of HA2 subunit of HA, which consequently facilitated the virus fusion process. Such findings offered an in-depth insight into the post-entry stage of IAV replication cycle. On the other hand, we also revealed the mechanism by which the host factor Ankyrin Repeat and BTB Domain Containing 1 (ABTB1) positively regulates the replication of IAV through promoting the nuclear import of the viral ribonucleoprotein (vRNP) complex. Mass spectrometry identified Tripartite Motif Containing 4 (TRIM4) as an interacting partner and downstream effector of ABTB1. TRIM4 mediated the K48-linked ubiquitination and proteasomal degradation of viral NP, thereby suppressing the nuclear import of the incoming vRNP complex and newly synthesized NP and impairing viral growth. Notably, ABTB1 mediated proteasomal degradation of TRIM4, which largely abolished the degradation of NP and impairment of viral growth mediated by TRIM4. Collectively, our data have deepened our understanding of the mechanisms by which host proteins affect the replication of IAV, which might help support the development of effective antiviral agents.
Co-Author(s)
Yuzhen Hu, Wenjun Shi, Li Jiang, Guangwen Wang, Hualan Chen, Chengjun Li
State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
Abstract Category
Transmission pathways, pathobiology, immune responses