A single-cell atlas reveals shared and distinct immune responses and metabolism during SARS-CoV-2 and HIV-1 infections

Abstract

SARS-CoV-2 and HIV-1 are RNA viruses that have killed millions of people worldwide. Understanding the similarities and differences between these two infections is critical for understanding disease progression and for developing effective vaccines and therapies, particularly for 38 million HIV-1+ individuals who are vulnerable to SARS-CoV-2 co-infection. Here, we utilized single-cell transcriptomics to perform a systematic comparison of 94,442 PBMCs from 7 COVID-19 and 9 HIV-1+ patients in an integrated immune atlas, in which 27 different cell types were identified using an accurate consensus single-cell annotation method. While immune cells in both cohorts show shared inflammation and disrupted mitochondrial function, COVID-19 patients exhibit stronger humoral immunity, broader IFN-I signaling, elevated Rho GTPase and mTOR pathway activities, and downregulated mitophagy. Our results elucidate transcriptional signatures associated with COVID-19 and HIV-1 that may reveal insights into fundamental disease biology and potential therapeutic targets to treat these viral infections.

Superantigens and SARS-CoV-2

“…We note a recent study of SARS-CoV-2 which found immunological dysfunction following mild to moderate infection, including depletion of naive T and B-cells in individuals with Long COVID [49], and a single cell atlas which also found depletion of naive T-cells and higher levels of apoptotic T-cells in SARS-CoV-2 infection than HIV [70]. Taken together with findings on post-SARS-CoV-2 autoantibodies [71,72], presentation of MIS-C [73], activation and depletion of T-cells [74] and a rise in IDDM [75], these are suggestive of a superantigen, superantigen-like protein or triggering of a superantigenic host response as a causative agent, and further research is needed into its role and likely long-term effects, particularly since SARS-CoV-2 has been found to persist in the body months after acute infection [76][77][78][79][80][81][82].…”

The Potential of Purinergic Signaling to Thwart Viruses Including SARS-CoV-2

“…phospholipase A 2 , p38 mitogen-activated kinase (p38MAPK) can activate reactive oxygen and nitrogen species and rho G proteins). Notably, elevated Rho GTPase and mTOR pathway activities were among features characterizing responses to SARS-CoV-2 that were distinct from those to HIV-1 infections (181). Data from corneal allograft rejection studies demonstrated that blockage of the ligand-gated ion channel P2X7 receptor suppressed Th1/Th17-mediated immune responses and NLRP3 inflammasome activation (182).…”