Influenza A virus subverts the LC3-pericentrin dynein adaptor complex for host cytoplasm entry.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40498831.
- Also identified by DOI 10.1126/sciadv.adu7602 and PMC identifier 12154174.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Influenza A virus (IAV) enters host cells via endocytosis, and fusion of the viral particles (VPs) at endosomes releases the viral ribonucleoproteins (vRNPs) into the cytoplasm. This uncoating step that is vital for IAV infection remains to be fully understood. The aggresome processing machinery (APM) plays a relevant but not essential role in this. Here, we reveal a mechanism in which light chain 3 proteins (LC3s) and pericentrin (PCNT) form an adaptor complex that is required for vRNPs binding to the dynein 1 and IAV uncoating at endosomes. This function of LC3s and PCNT is independent from their established role in autophagy and centrosome assembly, respectively. LC3s or PCNT depletion severely impairs IAV cytoplasm entry and infection, which can be further inhibited by additional silencing of histone deacetylase 6, an APM component. Collectively, our results show that IAV has adopted two redundant strategies to hijack the dynein biomolecular motors and facilitate VP uncoating.
Medical subject headings
- Influenza A virus
- Dyneins
- Microtubule-Associated Proteins
- Virus Internalization
- Cytoplasm
- Host-Pathogen Interactions
- Influenza, Human