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The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι.
Zhang, Yiwen; Chen, Yingshi; Li, Yuzhuang; Huang, Feng; Luo, Baohong; Yuan, Yaochang; Xia, Baijin; Ma, Xiancai; Yang, Tao; Yu, Fei; Liu, Jun; Liu, Bingfeng; Song, Zheng; Chen, Jingliang; Yan, Shumei; Wu, Liyang; Pan, Ting; Zhang, Xu; Li, Rong; Huang, Wenjing; He, Xin; Xiao, Fei; Zhang, Junsong; Zhang, Hui.
  • Zhang Y; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Chen Y; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Li Y; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Huang F; Department of Respiratory Diseases, Guangzhou Women and Children Hospital, 510010, Guangzhou, Guangdong, China.
  • Luo B; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Yuan Y; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Xia B; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Ma X; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Yang T; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Yu F; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Liu J; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Liu B; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Song Z; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Chen J; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Yan S; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Wu L; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Pan T; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Zhang X; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Li R; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Huang W; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 510000, Guangzhou, Guangdong, China.
  • He X; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Xiao F; Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, 519000, Zhuhai, Guangdong, China.
  • Zhang J; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 510000, Guangzhou, Guangdong, China; zhangh92@mail.sysu.edu.cn zhangjuns_0953@163.com.
  • Zhang H; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China; zhangh92@mail.sysu.edu.cn z
Proc Natl Acad Sci U S A ; 118(23)2021 06 08.
Article in English | MEDLINE | ID: covidwho-1238060
Semantic information from SemMedBD (by NLM)
1. 2019 novel coronavirus CAUSES COVID-19
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
COVID-19
2. DNA Sequence PART_OF SARS coronavirus
Subject
DNA Sequence
Predicate
PART_OF
Object
SARS coronavirus
3. DNA Sequence PART_OF 2019 novel coronavirus
Subject
DNA Sequence
Predicate
PART_OF
Object
2019 novel coronavirus
4. Viral Proteins INTERACTS_WITH PSMA6 gene|PSMA6
Subject
Viral Proteins
Predicate
INTERACTS_WITH
Object
PSMA6 gene|PSMA6
5. Homologous Gene AFFECTS Down-Regulation
Subject
Homologous Gene
Predicate
AFFECTS
Object
Down-Regulation
6. Antigen Presentation AFFECTS Immunologic Surveillance
Subject
Antigen Presentation
Predicate
AFFECTS
Object
Immunologic Surveillance
7. 2019 novel coronavirus CAUSES COVID-19
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
COVID-19
8. DNA Sequence PART_OF SARS coronavirus
Subject
DNA Sequence
Predicate
PART_OF
Object
SARS coronavirus
9. DNA Sequence PART_OF 2019 novel coronavirus
Subject
DNA Sequence
Predicate
PART_OF
Object
2019 novel coronavirus
10. Viral Proteins INTERACTS_WITH PSMA6 gene|PSMA6
Subject
Viral Proteins
Predicate
INTERACTS_WITH
Object
PSMA6 gene|PSMA6
11. Homologous Gene AFFECTS Down-Regulation
Subject
Homologous Gene
Predicate
AFFECTS
Object
Down-Regulation
12. Antigen Presentation AFFECTS Immunologic Surveillance
Subject
Antigen Presentation
Predicate
AFFECTS
Object
Immunologic Surveillance
ABSTRACT
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has claimed over 2 million lives worldwide. Although the genetic sequences of SARS-CoV and SARS-CoV-2 have high homology, the clinical and pathological characteristics of COVID-19 differ significantly from those of SARS. How and whether SARS-CoV-2 evades (cellular) immune surveillance requires further elucidation. In this study, we show that SARS-CoV-2 infection leads to major histocompability complex class Ι (MHC-Ι) down-regulation both in vitro and in vivo. The viral protein encoded by open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all viral proteins, directly interacts with MHC-Ι molecules and mediates their down-regulation. In ORF8-expressing cells, MHC-Ι molecules are selectively targeted for lysosomal degradation via autophagy. Thus, SARS-CoV-2-infected cells are much less sensitive to lysis by cytotoxic T lymphocytes. Because ORF8 protein impairs the antigen presentation system, inhibition of ORF8 could be a strategy to improve immune surveillance.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Proteins / Histocompatibility Antigens Class I / Down-Regulation / Antigen Presentation / Immune Evasion / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: Pnas.2024202118

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Proteins / Histocompatibility Antigens Class I / Down-Regulation / Antigen Presentation / Immune Evasion / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: Pnas.2024202118