title: Latently-infected CD4+ T cells are enriched for HIV-1 Tat variants with impaired transactivation activity.
abstract: 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.
authors.affiliation: University of California, San Francisco (UCSF) and San Francisco VA Medical Center (SFVAMC), 4150 Clement Street, 111W3, San Francisco, CA 94121, USA. steven.yukl@ucsf.edu
authors.forename: Steven
authors.initials: S
authors.lastname: Yukl
authors.forename: Satish
authors.initials: S
authors.lastname: Pillai
authors.forename: Peilin
authors.initials: P
authors.lastname: Li
authors.forename: Karen
authors.initials: K
authors.lastname: Chang
authors.forename: William
authors.initials: W
authors.lastname: Pasutti
authors.forename: Chris
authors.initials: C
authors.lastname: Ahlgren
authors.forename: Diane
authors.initials: D
authors.lastname: Havlir
authors.forename: Matthew
authors.initials: M
authors.lastname: Strain
authors.forename: Huldrych
authors.initials: H
authors.lastname: Günthard
authors.forename: Douglas
authors.initials: D
authors.lastname: Richman
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Rice
authors.forename: Eric
authors.initials: E
authors.lastname: Daar
authors.forename: Susan
authors.initials: S
authors.lastname: Little
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wong
mesh_terms: D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D018929:Cell Culture Techniques; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D006801:Humans; D014158:Transcription, Genetic / Q000276:immunology; D017735:Virus Latency / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D015696:Gene Products, tat