The single-cell landscape of immunological responses of CD4+ T cells in HIV versus severe acute respiratory syndrome coronavirus 2

Curr Opin HIV AIDS. 2021 Jan;16(1):36-47. doi: 10.1097/COH.0000000000000655.


Purpose of review: CD4 T cell loss is the hallmark of uncontrolled HIV-1 infection. Strikingly, CD4 T cell depletion is a strong indicator for disease severity in the recently emerged coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We reviewed recent single-cell immune profiling studies in HIV-1 infection and COVID-19 to provide critical insight in virus-induced immunopathogenesis.

Recent findings: Cytokine dysregulation in HIV-1 leads to chronic inflammation, while severe SARS-CoV-2 infection induces cytokine release syndrome and increased mortality. HIV-1-specific CD4 T cells are dysfunctional, while SARS-CoV-2-specific CD4 T cells exhibit robust Th1 function and correlate with protective antibody responses. In HIV-1 infection, follicular helper T cells (TFH) are susceptible to HIV-1 infection and persist in immune-sanctuary sites in lymphoid tissues as an HIV-1 reservoir. In severe SARS-CoV-2 infection, TFH are absent in lymphoid tissues and are associated with diminished protective immunity. Advancement in HIV-1 DNA, RNA, and protein-based single-cell capture methods can overcome the rarity and heterogeneity of HIV-1-infected cells and identify mechanisms of HIV-1 persistence and clonal expansion dynamics.

Summary: Single-cell immune profiling identifies a high-resolution picture of immune dysregulation in HIV-1 and SARS-CoV-2 infection and informs outcome prediction and therapeutic interventions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • COVID-19 / genetics
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Cytokines / genetics
  • Cytokines / immunology
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV Infections / virology
  • Humans
  • Pandemics
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*


  • Cytokines