期刊
NATURE MEDICINE
卷 20, 期 4, 页码 425-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3489
关键词
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资金
- Martin Delaney Collaboratory of AIDS Researchers for Eradication
- Delaney AIDS Research Enterprise (US National Institutes of Health) [AI096113, AI096109]
- Foundation for AIDS Research [108165-50-RGRL, 108707-54-RKRL]
- Johns Hopkins Center for AIDS Research
- US National Institutes of Health [43222]
- Howard Hughes Medical Institute
HIV-1 persists in a latent reservoir despite antiretroviral therapy (ART)(1-5). This reservoir is the major barrier to HIV-1 eradication(6,7). Current approaches to purging the latent reservoir involve pharmacologic induction of HIV-1 transcription and subsequent killing of infected cells by cytolytic T lymphocytes (CTLs) or viral cytopathic effects(8-10). Agents that reverse latency without activating T cells have been identified using in vitro models of latency. However, their effects on latently infected cells from infected individuals remain largely unknown. Using a new ex vivo assay, we demonstrate that none of the latency-reversing agents (LRAs) tested induced outgrowth of HIV-1 from the latent reservoir of patients on ART. Using a quantitative reverse transcription PCR assay specific for all HIV-1 mRNAs, we demonstrate that LRAs that do not cause T cell activation do not induce substantial increases in intracellular HIV-1 mRNA in patient cells; only the protein kinase C agonist bryostatin-1 caused significant increases. These findings demonstrate that current in vitro models do not fully recapitulate mechanisms governing HIV-1 latency in vivo. Further, our data indicate that non-activating LRAs are unlikely to drive the elimination of the latent reservoir in vivo when administered individually.
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