tetano
Editor, Senior Moderator
Cell Rep
. 2021 Jun 8;35(10):109213.
doi: 10.1016/j.celrep.2021.109213.
Mammalian cells use the autophagy process to restrict avian influenza virus replication
Siwen Liu[SUP] 1 [/SUP], Bobo Wing-Yee Mok[SUP] 1 [/SUP], Shaofeng Deng[SUP] 1 [/SUP], Honglian Liu[SUP] 1 [/SUP], Pui Wang[SUP] 1 [/SUP], Wenjun Song[SUP] 2 [/SUP], Pin Chen[SUP] 1 [/SUP], Xiaofeng Huang[SUP] 1 [/SUP], Min Zheng[SUP] 1 [/SUP], Siu-Ying Lau[SUP] 1 [/SUP], Conor J Cremin[SUP] 1 [/SUP], Chun-Yee Tam[SUP] 1 [/SUP], Baiying Li[SUP] 3 [/SUP], Liwen Jiang[SUP] 3 [/SUP], Yixin Chen[SUP] 4 [/SUP], Kwok-Yung Yuen[SUP] 1 [/SUP], Honglin Chen[SUP] 5 [/SUP]
Affiliations
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.
Keywords: M2; PB2; adaptation; autophagy; avian influenza; cross species transmission; host restriction; influenza; p62.
. 2021 Jun 8;35(10):109213.
doi: 10.1016/j.celrep.2021.109213.
Mammalian cells use the autophagy process to restrict avian influenza virus replication
Siwen Liu[SUP] 1 [/SUP], Bobo Wing-Yee Mok[SUP] 1 [/SUP], Shaofeng Deng[SUP] 1 [/SUP], Honglian Liu[SUP] 1 [/SUP], Pui Wang[SUP] 1 [/SUP], Wenjun Song[SUP] 2 [/SUP], Pin Chen[SUP] 1 [/SUP], Xiaofeng Huang[SUP] 1 [/SUP], Min Zheng[SUP] 1 [/SUP], Siu-Ying Lau[SUP] 1 [/SUP], Conor J Cremin[SUP] 1 [/SUP], Chun-Yee Tam[SUP] 1 [/SUP], Baiying Li[SUP] 3 [/SUP], Liwen Jiang[SUP] 3 [/SUP], Yixin Chen[SUP] 4 [/SUP], Kwok-Yung Yuen[SUP] 1 [/SUP], Honglin Chen[SUP] 5 [/SUP]
Affiliations
- PMID: 34107256
- DOI: 10.1016/j.celrep.2021.109213
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.
Keywords: M2; PB2; adaptation; autophagy; avian influenza; cross species transmission; host restriction; influenza; p62.