Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion. Journal of medical virology Huang, H., Wang, S., Fang, G., Chou, W., Liao, C., Sun, C., Jan, J., Ma, H., Ko, H., Ko, Y., Chiang, M., Liang, J., Kuo, C., Lee, T., Morales-Scheihing, D., Shen, C., Chen, S., McCullough, L. D., Cui, L., Wernig, G., Tao, M., Lin, Y., Chang, Y., Wang, S., Lai, Y., Li, C. 2023


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 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 (TO-GCN) 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 NF-kappaB and IRF1 pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 ChIP-sequencing. Cross-referencing our transcriptomic and epigenomic datasets revealed that coupling NF-kappaB and IRF1 pathways mediate 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-kappaB and IRF1-PD-L1 axis may represent an alternative strategy to reduce COVID-19 severity. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/jmv.28478

View details for PubMedID 36609964