2. Academic Validation
  3. Influenza A virus subverts the LC3-pericentrin dynein adaptor complex for host cytoplasm entry

Influenza A virus subverts the LC3-pericentrin dynein adaptor complex for host cytoplasm entry

  • Sci Adv. 2025 Jun 13;11(24):eadu7602. doi: 10.1126/sciadv.adu7602.
Yingying Cong 1 2 3,  Pauline Verlhac 3,  Benjamin B Green 4,  Jacqueline de Vries-Idema 5,  Line Moesgaard Strauss 1,  Clàudia Río-Bergé 1,  Anders Etzerodt 1,  Lene N Nejsum 4,  Anke L W Huckriede 5,  Fulvio Reggiori 1 3 6
Affiliations

Affiliations

  • 1 Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • 2 Department of Drug Design, University of Groningen, Groningen, Netherlands.
  • 3 Department of Biomedical Sciences, University of Groningen, University Medical Center Groningen (UMCG), University of Groningen, Groningen, Netherlands.
  • 4 Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • 5 Department of Medical Microbiology and Infection Prevention, UMCG, University of Groningen, Groningen, Netherlands.
  • 6 Aarhus Institute of Advanced Studies (AIAS), Aarhus University, Aarhus, Denmark.
PMID: 40498831 DOI: 10.1126/sciadv.adu7602
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.

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