The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι

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Significance

We report that SARS-CoV-2 utilizes its ORF8 protein as a unique mechanism to alter the expression of surface MHC-Ι expression to evade immune surveillance. Our study is significant for providing an understanding of the pathogenesis of SARS-CoV-2 and will provide additional perspective to the intensive ongoing investigation into the mechanism and function of T cell antiviral immunity in COVID-19.

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.

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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A Novel Coronavirus from Patients with Pneumonia in China, 2019

Na Zhu, Dingyu Zhang, Wenling Wang … (2020)

Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)

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Is Open Access

MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability

Kazutaka Katoh, Daron Standley (2013)

We report a major update of the MAFFT multiple sequence alignment program. This version has several new features, including options for adding unaligned sequences into an existing alignment, adjustment of direction in nucleotide alignment, constrained alignment and parallel processing, which were implemented after the previous major update. This report shows actual examples to explain how these features work, alone and in combination. Some examples incorrectly aligned by MAFFT are also shown to clarify its limitations. We discuss how to avoid misalignments, and our ongoing efforts to overcome such limitations.

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Author and article information

Journal

Journal ID (nlm-ta): Proc Natl Acad Sci U S A

Journal ID (iso-abbrev): Proc Natl Acad Sci U S A

Journal ID (hwp): pnas

Journal ID (publisher-id): PNAS

Title: Proceedings of the National Academy of Sciences of the United States of America

Publisher: National Academy of Sciences

ISSN (Print): 0027-8424

ISSN (Electronic): 1091-6490

Publication date (Print): 08 June 2021

Publication date (Electronic): 21 May 2021

Publication date PMC-release: 21 May 2021

Volume: 118

Issue: 23

Electronic Location Identifier: e2024202118

Affiliations

[1] ^aInstitute 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;

[2] ^bDepartment of Respiratory Diseases, Guangzhou Women and Children Hospital , 510010, Guangzhou, Guangdong, China;

[3] ^cGuangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences , 510000, Guangzhou, Guangdong, China;

[4] ^dDepartment of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University , 519000, Zhuhai, Guangdong, China

Author notes

¹To whom correspondence may be addressed. Email: zhangh92@ 123456mail.sysu.edu.cn or zhangjuns_0953@ 123456163.com .

Edited by Stephen P. Goff, Columbia University Medical Center, New York, NY, and approved April 5, 2021 (received for review November 23, 2020)

Author contributions: Y.Z., J.Z., and H.Z. designed research; Y.Z., Y.C., Y.L., F.H., B. Luo, Y.Y., B.X., X.M., T.Y., F.Y., J.L., B. Liu, Z.S., J.C., S.Y., L.W., T.P., R.L., W.H., and J.Z. performed research; F.X. contributed new reagents/analytic tools; Y.Z., X.Z., and X.H. analyzed data; and Y.Z. and H.Z. wrote the paper.

Author information

Yiwen Zhang https://orcid.org/0000-0002-5232-0335

Xiancai Ma https://orcid.org/0000-0002-4934-4221

Bingfeng Liu https://orcid.org/0000-0003-1278-727X

Xin He https://orcid.org/0000-0002-2131-2092

Hui Zhang https://orcid.org/0000-0003-3620-610X

Article

Publisher ID: 202024202

DOI: 10.1073/pnas.2024202118

PMC ID: 8201919

PubMed ID: 34021074

SO-VID: 88183b3a-a678-42a6-a467-cfecf7566c2f

License:

This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

History

Page count

Pages: 12