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

Charlene Wang; Mohamed Abdel-Mohsen; Matthew C. Strain; Steven M. Lada; Steven Yukl; Leslie R. Cockerham; Christopher D. Pilcher; Frederick M. Hecht; Elizabeth Sinclair; Teri Liegler; Douglas D. Richman; Steven G. Deeks; Satish K. Pillai

doi:10.1093/infdis/jiu338

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

Charlene Wang, Mohamed Abdel-Mohsen, Matthew C. Strain, Steven M. Lada, Steven Yukl, Leslie R. Cockerham, Christopher D. Pilcher, Frederick M. Hecht, Elizabeth Sinclair, Teri Liegler, Douglas D. Richman, Steven G. Deeks, Satish K. Pillai^*

^*Corresponding author for this work

Medicine, Infectious Diseases Division

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1838-1843
Number of pages	6
Journal	Journal of Infectious Diseases
Volume	210
Issue number	11
DOIs	https://doi.org/10.1093/infdis/jiu338
State	Published - Dec 1 2014

Funding

Keywords

CCR5
Coreceptor
Eradication
HIV
HIV replication
HIV transcription
Latency
NF-κB
Reservoir
Δ32

ASJC Scopus subject areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/infdis/jiu338

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Wang, C., Abdel-Mohsen, M., Strain, M. C., Lada, S. M., Yukl, S., Cockerham, L. R., Pilcher, C. D., Hecht, F. M., Sinclair, E., Liegler, T., Richman, D. D., Deeks, S. G., & Pillai, S. K. (2014). Decreased HIV type 1 transcription in CCR5-Δ32 heterozygotes during suppressive antiretroviral therapy. Journal of Infectious Diseases, 210(11), 1838-1843. https://doi.org/10.1093/infdis/jiu338

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title = "Decreased HIV type 1 transcription in CCR5-Δ32 heterozygotes during suppressive antiretroviral therapy",

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, Coreceptor, Eradication, HIV, HIV replication, HIV transcription, Latency, NF-κB, Reservoir, Δ32",

author = "Charlene Wang and Mohamed Abdel-Mohsen and Strain, {Matthew C.} and Lada, {Steven M.} and Steven Yukl and Cockerham, {Leslie R.} and Pilcher, {Christopher D.} and Hecht, {Frederick M.} and Elizabeth Sinclair and Teri Liegler and Richman, {Douglas D.} and Deeks, {Steven G.} and Pillai, {Satish K.}",

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Wang, C, Abdel-Mohsen, M, Strain, MC, Lada, SM, Yukl, S, Cockerham, LR, Pilcher, CD, Hecht, FM, Sinclair, E, Liegler, T, Richman, DD, Deeks, SG & Pillai, SK 2014, 'Decreased HIV type 1 transcription in CCR5-Δ32 heterozygotes during suppressive antiretroviral therapy', Journal of Infectious Diseases, vol. 210, no. 11, pp. 1838-1843. https://doi.org/10.1093/infdis/jiu338

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T1 - Decreased HIV type 1 transcription in CCR5-Δ32 heterozygotes during suppressive antiretroviral therapy

AU - Wang, Charlene

AU - Abdel-Mohsen, Mohamed

AU - Strain, Matthew C.

AU - Lada, Steven M.

AU - Yukl, Steven

AU - Cockerham, Leslie R.

AU - Pilcher, Christopher D.

AU - Hecht, Frederick M.

AU - Sinclair, Elizabeth

AU - Liegler, Teri

AU - Richman, Douglas D.

AU - Deeks, Steven G.

AU - Pillai, Satish K.

N1 - Publisher Copyright: © The Author 2014.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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.

AB - 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.

KW - CCR5

KW - Coreceptor

KW - Eradication

KW - HIV

KW - HIV replication

KW - HIV transcription

KW - Latency

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KW - Reservoir

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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