HIV rapidly targets a diverse pool of CD4+ T cells to establish productive and latent infections

Immunity. 2023 Mar 14;56(3):653-668.e5. doi: 10.1016/j.immuni.2023.01.030. Epub 2023 Feb 17.


Upon infection, HIV disseminates throughout the human body within 1-2 weeks. However, its early cellular targets remain poorly characterized. We used a single-cell approach to retrieve the phenotype and TCR sequence of infected cells in blood and lymphoid tissue from individuals at the earliest stages of HIV infection. HIV initially targeted a few proliferating memory CD4+ T cells displaying high surface expression of CCR5. The phenotype of productively infected cells differed by Fiebig stage and between blood and lymph nodes. The TCR repertoire of productively infected cells was heavily biased, with preferential infection of previously expanded and disseminated clones, but composed almost exclusively of unique clonotypes, indicating that they were the product of independent infection events. Latent genetically intact proviruses were already archived early in infection. Hence, productive infection is initially established in a pool of phenotypically and clonotypically distinct T cells, and latently infected cells are generated simultaneously.

Keywords: HIV; HIV reservoir; acute infection; clonal expansion; inducibility; latency; lymph nodes; memory CD4(+) T cells; productive infection; proliferation.

Publication types

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

MeSH terms

  • CD4-Positive T-Lymphocytes / metabolism
  • HIV Infections*
  • HIV-1* / genetics
  • Humans
  • Latent Infection* / metabolism
  • Latent Infection* / pathology
  • Receptors, Antigen, T-Cell / metabolism
  • Virus Latency


  • Receptors, Antigen, T-Cell