Mammalian cells use the autophagy process to restrict avian influenza virus replication

Siwen Liu, Bobo Wing Yee Mok, Shaofeng Deng, Honglian Liu, Pui Wang, Wenjun Song, Pin Chen, Xiaofeng Huang, Min Zheng, Siu Ying Lau, Conor J. Cremin, Chun Yee Tam, Baiying Li, Liwen Jiang, Yixin Chen, Kwok Yung Yuen, Honglin Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

16 Citations (Scopus)

Abstract

Host adaptive mutations in the influenza A virus (IAV) PB2 protein are critical for human infection, but their molecular action is not well understood. We observe that when IAV containing avian PB2 infects mammalian cells, viral ribonucleoprotein (vRNP) aggregates that localize to the microtubule-organizing center (MTOC) are formed. These vRNP aggregates resemble LC3B-associated autophagosome structures, with aggresome-like properties, in that they cause the re-distribution of vimentin. However, electron microscopy reveals that these aggregates represent an accumulation of autophagic vacuoles. Compared to mammalian-PB2 virus, avian-PB2 virus induces higher autophagic flux in infected cells, indicating an increased rate of autophagosomes containing avian vRNPs fusing with lysosomes. We found that p62 is essential for the formation of vRNP aggregates and that the Raptor-interacting region of p62 is required for interaction with vRNPs through the PB2 polymerase subunit. Selective autophagic sequestration during late-stage virus replication is thus an additional strategy for host restriction of avian-PB2 IAV.

Original languageEnglish
Article number109213
Number of pages14
JournalCell Reports
Volume35
Issue number10
DOIs
Publication statusPublished - 8 Jun 2021

Scopus Subject Areas

  • Biochemistry, Genetics and Molecular Biology(all)

User-Defined Keywords

  • adaptation
  • autophagy
  • avian influenza
  • cross species transmission
  • host restriction
  • influenza
  • M2
  • p62
  • PB2

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