Your browser doesn't support javascript.
ORF3a-Mediated Incomplete Autophagy Facilitates Severe Acute Respiratory Syndrome Coronavirus-2 Replication.
Qu, Yafei; Wang, Xin; Zhu, Yunkai; Wang, Weili; Wang, Yuyan; Hu, Gaowei; Liu, Chengrong; Li, Jingjiao; Ren, Shanhui; Xiao, Maggie Z X; Liu, Zhenshan; Wang, Chunxia; Fu, Joyce; Zhang, Yucai; Li, Ping; Zhang, Rong; Liang, Qiming.
  • Qu Y; Research Center of Translational Medicine, Shanghai Institute of Immunology, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wang X; Research Center of Translational Medicine, Shanghai Institute of Immunology, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhu Y; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Science, Shanghai Medical College, Biosafety Level 3 Laboratory, Fudan University, Shanghai, China.
  • Wang W; Research Center of Translational Medicine, Shanghai Institute of Immunology, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wang Y; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Science, Shanghai Medical College, Biosafety Level 3 Laboratory, Fudan University, Shanghai, China.
  • Hu G; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Science, Shanghai Medical College, Biosafety Level 3 Laboratory, Fudan University, Shanghai, China.
  • Liu C; Research Center of Translational Medicine, Shanghai Institute of Immunology, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Li J; Research Center of Translational Medicine, Shanghai Institute of Immunology, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Ren S; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Science, Shanghai Medical College, Biosafety Level 3 Laboratory, Fudan University, Shanghai, China.
  • Xiao MZX; Faculty of Medicine, University of Alberta, Edmonton, AB, Canada.
  • Liu Z; Research Center of Translational Medicine, Shanghai Institute of Immunology, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wang C; Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
  • Fu J; Department of Statistics, University of California, Riverside, Riverside, CA, United States.
  • Zhang Y; Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
  • Li P; Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, China.
  • Zhang R; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Science, Shanghai Medical College, Biosafety Level 3 Laboratory, Fudan University, Shanghai, China.
  • Liang Q; Research Center of Translational Medicine, Shanghai Institute of Immunology, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Cell Dev Biol ; 9: 716208, 2021.
Article in English | MEDLINE | ID: covidwho-1354835
ABSTRACT
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent for the coronavirus disease 2019 (COVID-19) pandemic and there is an urgent need to understand the cellular response to SARS-CoV-2 infection. Beclin 1 is an essential scaffold autophagy protein that forms two distinct subcomplexes with modulators Atg14 and UVRAG, responsible for autophagosome formation and maturation, respectively. In the present study, we found that SARS-CoV-2 infection triggers an incomplete autophagy response, elevated autophagosome formation but impaired autophagosome maturation, and declined autophagy by genetic knockout of essential autophagic genes reduces SARS-CoV-2 replication efficiency. By screening 26 viral proteins of SARS-CoV-2, we demonstrated that expression of ORF3a alone is sufficient to induce incomplete autophagy. Mechanistically, SARS-CoV-2 ORF3a interacts with autophagy regulator UVRAG to facilitate PI3KC3-C1 (Beclin-1-Vps34-Atg14) but selectively inhibit PI3KC3-C2 (Beclin-1-Vps34-UVRAG). Interestingly, although SARS-CoV ORF3a shares 72.7% amino acid identity with the SARS-CoV-2 ORF3a, the former had no effect on cellular autophagy response. Thus, our findings provide the mechanistic evidence of possible takeover of host autophagy machinery by ORF3a to facilitate SARS-CoV-2 replication and raise the possibility of targeting the autophagic pathway for the treatment of COVID-19.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: Front Cell Dev Biol Year: 2021 Document Type: Article Affiliation country: Fcell.2021.716208

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: Front Cell Dev Biol Year: 2021 Document Type: Article Affiliation country: Fcell.2021.716208