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

The study “A single-cell atlas reveals shared and distinct immune responses and metabolism during SARS-CoV-2 and HIV-1 infections” provides a detailed comparison of the immune responses in COVID-19 and HIV-1 patients using single-cell transcriptomics.

Here are the key findings and highlights:

  1. Background and Motivation: SARS-CoV-2 and HIV-1 are both RNA viruses with significant mortality and morbidity impacts. Despite similarities, they differ in their progression and host immune response. This study aims to understand these differences at a cellular level, which could inform treatment strategies, especially for HIV-1+ individuals vulnerable to COVID-19​​.
  2. Methodology: The study analyzed peripheral blood mononuclear cells (PBMCs) from 7 severe COVID-19 and 9 HIV-1+ patients. A comprehensive immune profiling was done using an integrated annotation strategy combining manual annotation, correlation-based label transfer, and deep-learning classification. This resulted in identifying 27 different cell types, improving the resolution compared to previous studies​​.
  3. Comparative Analysis: COVID-19 and HIV-1+ patients showed disease-specific immune signatures. COVID-19 patients exhibited stronger humoral immunity, broader interferon type I (IFN-I) signaling, elevated Rho GTPase and mTOR pathway activities, and downregulated mitophagy, compared to HIV-1+ patients. Both groups shared inflammation and disrupted mitochondrial function​​.
  4. Gene Expression: Differential gene expression analysis highlighted distinct sets of differentially expressed genes (DEGs) in COVID-19 and HIV-1+ patients. COVID-19 patients showed upregulation of genes involved in the type-I interferon signaling pathway and downregulation of genes in the AP-1 transcription factor pathway. HIV-1+ patients exhibited upregulation of genes associated with antiviral response and inflammation​​.
  5. Innate Immune Cells: The study found that innate immune cells like monocytes and dendritic cells (DCs) play vital roles in both diseases, with significant differences in their activity and interaction with the adaptive immune system. COVID-19 patients displayed more active and cytotoxic innate immune cells, while HIV-1+ patients showed a different pattern of cytokine and chemokine expression​​.
  6. Humoral Response: COVID-19 patients had a stronger plasmablast and antibody response than HIV-1+ patients. The study identified distinct subpopulations of B cells and plasmablasts in each disease, with COVID-19 patients showing higher proliferation and maturation of plasmablasts. Both diseases exhibited a shift away from homeostasis in B cells, with differentially expressed genes related to apoptosis, activation, and antibody diversity​​.
  7. T Cell Response: An increase in IFN-I+ CD4+ T cells was observed in both patient groups. However, COVID-19 patients had a higher proportion of these cells, as well as a distinct subpopulation of cytotoxic CD4+ T cells. The study also reported a decrease in naïve T cells and an enrichment of effector memory T cells in both diseases, with variations in T-cell activation-associated genes​​.
  8. IFN-I Signaling: IFN-I signaling was upregulated in both diseases, but with disease-specific gene expression differences. COVID-19 patients showed enriched pathways in MAPK signaling and interleukin signaling, linked to inflammation and cytokine storm, among others. This highlights distinct biological functions of IFN-I response in COVID-19 versus HIV-1​​.

In summary, the study provides a comprehensive analysis of the immune response in COVID-19 and HIV-1, revealing distinct cellular and molecular profiles, which could be instrumental in understanding disease mechanisms and developing targeted therapies.

Read More: https://www.biorxiv.org/content/10.1101/2022.01.10.475725v1

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