J Med Virol. 2025 Nov;97(11):e70714. doi: 10.1002/jmv.70714.
ABSTRACT
The human enterovirus A71 (EV-A71) is known to infect host cells, replicate, and assemble viral particles, which are released by cell lysis. However, studies have demonstrated that EV-A71 can also exit cells via a non-lytic pathway. Nevertheless, research on this phenomenon remains limited. The present study aims to elucidate the mechanisms by which EV-A71 employs non-lytic pathways to release viral particles. A combination of mass spectrometry and gene ontology analysis was utilized to identify the host protein IQGAP1 as interacting with the EV-A71 3CD protein. The extracellular vesicles released from EV-A71-infected cells with IQGAP1 knockdown exhibited diminished expression of both IQGAP1 and EV-A71 VP1 proteins, accompanied by a substantial decrease in Tsg101 level. In IQGAP1 knockout cells or after dihydroartemisinin-mediated IQGAP1 inhibition, unclosed phagosomes were observed, impairing viral particle release. Furthermore, IQGAP1 has been found to facilitate the closure of phagosomes, thus forming virus-containing autophagosomes and promoting the non-lytic release of EV-A71 particles. The mechanism of action of the EV-A71 virus involves the exploitation of a host cell’s IQGAP1 to regulate autophagy, leading to the formation of virus-containing autophagosomes. This process ultimately results in the promotion of non-lytic viral particle release.
PMID:41251103 | DOI:10.1002/jmv.70714
