PD-L1, the culprit of lymphopenia in COVID-19 patients
Patients with severe COVID-19 often suffer from lymphopenia, which is linked to cytokine storm and mortality. However, it remains largely unknown how SARS-CoV-2 cripples immune system. The research groups, Dr. Chia-Wei Li, Dr. Shu-Ping Wang, and Dr. Yao-Ming Chang, in the IBMS at Academia Sinica explored the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. They adopted a reverse time-order gene coexpression network (TO-GCN) to analyze time-series RNA-seq, revealing epigenetic modifications at the late stage of viral egress. Cross-referencing the two datasets revealed that SARS-CoV-2 couples NF-κB and IRF1 pathways to upregulate PD-L1. In collaboration with Dr. Louise D. McCullough and Dr. Gerlinde Wernig, PD-L1 expression has a strong correlation with the severity of COVID-19 in patient samples. Blocking PD-L1 at an early stage of virally-infected mice significantly reduce virus infection. Thus, targeting the SARS-CoV-2-mediated PD-L1 may represent an alternative strategy to reduce COVID-19 infection.
The study entitled “Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion” is recently published online in Journal of medical virology.
Article link (Journal of medical virology): https://onlinelibrary.wiley.com/doi/10.1002/jmv.28478