Latently-infected CD4+ T cells are enriched for HIV-1 Tat variants with impaired transactivation activity

Virology. 2009 Apr 25;387(1):98-108. doi: 10.1016/j.virol.2009.01.013. Epub 2009 Mar 5.


The ability of HIV to establish latent infection in CD4+ lymphocytes represents a major barrier to the eradication of HIV. It is not clear what mechanisms favor latent over productive infection, but prior studies have suggested a role for the viral transcription factor Tat or its RNA target, TAR. Using samples from five individuals who were started on ART within 6 months of infection and achieved a viral load <50 (suppressed), we isolated one- and two-exon tat RNA from HIV propagated ex vivo from baseline plasma and from co-cultures of CD4+ T cells obtained at baseline and suppressed time points. Compared to virus from the baseline plasma (mostly from productively-infected CD4+ T cells), virus from the baseline and suppressed co-cultures (mostly from latently-infected cells) had more Tat variants with impaired transactivation activity. These findings suggest that impaired activity in the Tat-TAR axis may contribute to the establishment of latent infection in CD4+ T cells.

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 Antigens / genetics
  • CD4 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Culture Techniques
  • Gene Products, tat / genetics
  • Gene Products, tat / metabolism*
  • HIV Infections / blood
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / genetics*
  • HIV-1 / immunology
  • HIV-1 / physiology*
  • Humans
  • Transcription, Genetic / immunology
  • Virus Latency* / immunology


  • CD4 Antigens
  • Gene Products, tat