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J Infect Dis. 2014 Dec 1;210(11):1838-43. doi: 10.1093/infdis/jiu338. Epub 2014 Jun 16.

Decreased HIV type 1 transcription in CCR5-Δ32 heterozygotes during suppressive antiretroviral therapy.

Author information

1
Emory University, Atlanta, Georgia Blood Systems Research Institute.
2
Blood Systems Research Institute University of California-San Francisco.
3
University of California-San Diego Veterans Affairs San Diego Healthcare System, California.
4
University of California-San Francisco San Francisco Veterans Affairs Medical Center.
5
University of California-San Francisco.

Abstract

Individuals who are heterozygous for the CCR5-Δ32 mutation provide a natural model to examine the effects of reduced CCR5 expression on human immunodeficiency virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Δ32 heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral therapy. Cell-associated HIV RNA levels (P=.035), RNA to DNA transcriptional ratios (P=.013), and frequency of detectable HIV 2-long terminal repeat circular DNA (P=.013) were significantly lower in CD4+ T cells from CCR5-Δ32 heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5 surface expression on CD4+ T cells (r2=0.136; P=.002). Our findings suggest that curative strategies should further explore manipulation of CCR5.

KEYWORDS:

CCR5; HIV; HIV replication; HIV transcription; NF-κB; coreceptor; eradication; latency; reservoir; Δ32

PMID:
24935955
PMCID:
PMC4271057
DOI:
10.1093/infdis/jiu338
[Indexed for MEDLINE]
Free PMC Article

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