Intra- and extra-cellular environments contribute to the fate of HIV-1 infection

Cell Rep. 2021 Aug 31;36(9):109622. doi: 10.1016/j.celrep.2021.109622.


HIV-1 entry into host cells leads to one of the following three alternative fates: (1) HIV-1 elimination by restriction factors, (2) establishment of HIV-1 latency, or (3) active viral replication in target cells. Here, we report the development of an improved system for monitoring HIV-1 fate at single-cell and population levels and show the diverse applications of this system to study specific aspects of HIV-1 fate in different cell types and under different environments. An analysis of the transcriptome of infected, primary CD4+ T cells that support alternative fates of HIV-1 identifies differential gene expression signatures in these cells. Small molecules are able to selectively target cells that support viral replication with no significant effect on viral latency. In addition, HIV-1 fate varies in different tissues following infection of humanized mice in vivo. Altogether, these studies indicate that intra- and extra-cellular environments contribute to the fate of HIV-1 infection.

Keywords: HIV-1 fate; HIV-1 latency; humanized mouse model; transcriptomic analysis.

Publication types

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

MeSH terms

  • Animals
  • Anti-HIV Agents / pharmacology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology*
  • Cellular Microenvironment*
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • HEK293 Cells
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / drug effects
  • HIV-1 / growth & development
  • HIV-1 / immunology
  • HIV-1 / pathogenicity*
  • Host-Pathogen Interactions
  • Humans
  • Mice, Inbred NOD
  • Mice, SCID
  • THP-1 Cells
  • Transcriptome
  • Virus Internalization
  • Virus Latency
  • Virus Replication


  • Anti-HIV Agents