Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion.

Autor: Huang HC; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Wang SH; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Fang GC; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Chou WC; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Liao CC; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Sun CP; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Jan JT; Genomics Research Center, Academia Sinica, Taipei, Taiwan., Ma HH; Genomics Research Center, Academia Sinica, Taipei, Taiwan., Ko HY; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Ko YA; Biomedical Translational Research Center, Academia Sinica, Taipei, Taiwan., Chiang MT; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Liang JJ; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Kuo CT; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Lee TA; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Morales-Scheihing D; Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA., Shen CY; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Chen SY; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., McCullough LD; Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA., Cui L; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Medical Center, Stanford, California, USA., Wernig G; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Medical Center, Stanford, California, USA., Tao MH; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.; Biomedical Translational Research Center, Academia Sinica, Taipei, Taiwan., Lin YL; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.; Biomedical Translational Research Center, Academia Sinica, Taipei, Taiwan., Chang YM; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Wang SP; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Lai YJ; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.; Solomont School of Nursing, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, Lowell, Massachusetts, USA., Li CW; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Jazyk: angličtina
Zdroj: Journal of medical virology [J Med Virol] 2023 Feb; Vol. 95 (2), pp. e28478.
DOI: 10.1002/jmv.28478
Abstrakt: Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T-cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. We adopted a reverse time-order gene coexpression network approach to analyze time-series RNA-sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS-CoV-2-activated nuclear factor-κB (NF-κB) and interferon regulatory factor 1 (IRF1) pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 chromatin immunoprecipitation sequencing. Cross-referencing our transcriptomic and epigenomic data sets revealed that coupling NF-κB and IRF1 pathways mediate programmed death ligand-1 (PD-L1) immunosuppressive programs. Interestingly, we observed higher PD-L1 expression in Omicron-infected cells than SARS-CoV-2 infected cells. Blocking PD-L1 at an early stage of virally-infected AAV-hACE2 mice significantly recovered lymphocyte counts and lowered inflammatory cytokine levels. Our findings indicate that targeting the SARS-CoV-2-mediated NF-κB and IRF1-PD-L1 axis may represent an alternative strategy to reduce COVID-19 severity.
(© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: