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.
authors.affiliation: Emory University, Atlanta, Georgia Blood Systems Research Institute.
authors.forename: Charlene
authors.initials: C
authors.lastname: Wang
authors.affiliation: Blood Systems Research Institute University of California-San Francisco.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Mohsen
authors.affiliation: University of California-San Diego Veterans Affairs San Diego Healthcare System, California.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Strain
authors.affiliation: University of California-San Diego Veterans Affairs San Diego Healthcare System, California.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Lada
authors.affiliation: University of California-San Francisco San Francisco Veterans Affairs Medical Center.
authors.forename: Steven
authors.initials: S
authors.lastname: Yukl
authors.affiliation: University of California-San Francisco.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Cockerham
authors.affiliation: University of California-San Francisco.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pilcher
authors.affiliation: University of California-San Francisco.
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.affiliation: University of California-San Francisco.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.affiliation: University of California-San Francisco.
authors.forename: Teri
authors.initials: T
authors.lastname: Liegler
authors.affiliation: University of California-San Diego Veterans Affairs San Diego Healthcare System, California.
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.affiliation: University of California-San Francisco.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: Blood Systems Research Institute University of California-San Francisco.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Pillai
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015331:Cohort Studies; D015967:Gene Expression Regulation, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D010641:Phenotype; D012367:RNA, Viral / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics*; D019562:Viral Load
chemical_list: D012367:RNA, Viral; D019713:Receptors, CCR5
keywords: CCR5; HIV; HIV replication; HIV transcription; NF-κB; coreceptor; eradication; latency; reservoir; Δ32