title: Gene expression and viral prodution in latently infected, resting CD4+ T cells in viremic versus aviremic HIV-infected individuals.
abstract: The presence of HIV-1 in latently infected, resting CD4(+) T cells has been clearly demonstrated in infected individuals; however, the extent of viral expression and the underlying mechanisms of the persistence of HIV-1 in this viral reservoir have not been fully delineated. Here, we show that resting CD4(+) T cells from the majority of viremic patients are capable of producing cell-free HIV-1 spontaneously ex vivo. The levels of HIV-1 released by resting CD4(+) T cells were not significantly reduced in the presence of inhibitors of cellular proliferation and viral replication. However, resting CD4(+) T cells from the majority of aviremic patients failed to produce virions, despite levels of HIV-1 proviral DNA and cell-associated HIV-1 RNA comparable to viremic patients. The DNA microarray analysis demonstrated that a number of genes involving transcription regulation, RNA processing and modification, and protein trafficking and vesicle transport were significantly upregulated in resting CD4(+) T cells of viremic patients compared to those of aviremic patients. These results suggest that active viral replication has a significant impact on the physiologic state of resting CD4(+) T cells in infected viremic patients and, in turn, allows release of HIV-1 without exogenous activation stimuli. In addition, given that no quantifiable virions were produced by the latent viral reservoir in the majority of aviremic patients despite the presence of cell-associated HIV-1 RNA, evidence for transcription of HIV-1 RNA in resting CD4(+) T cells of aviremic patients should not necessarily be taken as direct evidence for ongoing viral replication during effective therapy.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. twchun@nih.gov
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chun
authors.forename: J Shawn
authors.initials: JS
authors.lastname: Justement
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Glynn
authors.initials: G
authors.lastname: Dennis
authors.forename: Claire W
authors.initials: CW
authors.lastname: Hallahan
authors.forename: Christina
authors.initials: C
authors.lastname: Sanford
authors.forename: Punita
authors.initials: P
authors.lastname: Pandya
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
authors.forename: Mary
authors.initials: M
authors.lastname: McLaughlin
authors.forename: Linda A
authors.initials: LA
authors.lastname: Ehler
authors.forename: Susan
authors.initials: S
authors.lastname: Moir
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D017931:DNA Primers; D004279:DNA, Viral; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000235:genetics / Q000821:virology*; D018023:HIV Seronegativity / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D014766:Viremia; D014779:Virus Replication
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; D012367:RNA, Viral