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Cited by 488

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo

Open access
Bullen, C Korin, Laird, Gregory M, Durand, Christine M, Siliciano, Janet D, Siliciano, Robert F·2014·Nature Medicine

Abstract

HIV-1 persists in a latent reservoir despite antiretroviral therapy (ART). This reservoir is the major barrier to HIV-1 eradication. 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. 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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Metadata

Authors
Bullen, C. K., Laird, G. M., Durand, C. M., Siliciano, J. D., & Siliciano, R. F.
Venue
Nature Medicine
Published
2014-03-23
Volume
20
Issue
4
Pages
425-429
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2038598840
Cited by
488
References
5
FWCI
29.01
Type
journal article
Language
en
Open access
green

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