title: Efficiency of CCR5 coreceptor utilization by the HIV quasispecies increases over time, but is not associated with disease progression.
abstract: CCR5 is the primary coreceptor for HIV entry. Early after infection, the HIV viral population diversifies rapidly into a quasispecies. It is not known whether the initial efficiency of the viral quasispecies to utilize CCR5 is associated with HIV disease progression or if it changes in an infected individual over time. The CCR5 and CXCR4 utilization efficiencies (R5-UE and X4-UE) of the HIV quasispecies were examined using a pseudovirus, single-round infection assay for samples obtained from known seroconverters from Rakai district, Uganda (n=88). Initial and longitudinal R5-UE values were examined to assess the association of R5-UE with HIV disease progression using multivariate Cox proportional hazard models. Longitudinal samples were analyzed for 35 seroconverters who had samples available from multiple time points. There was no association between initial or longitudinal changes in R5-UE and the hazard of HIV disease progression (p=0.225 and p=0.942, respectively). In addition, R5-UE increased significantly over time after HIV seroconversion (p<0.001), regardless of HIV subtype or the emergence of CXCR4-tropic virus. These data demonstrate that the R5-UE of the viral quasispecies early in HIV infection is not associated with disease progression, and that R5-UE levels increase in HIV-infected individuals over time.
authors.affiliation: Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Redd
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Kong
authors.forename: Noah
authors.initials: N
authors.lastname: Kiwanuka
authors.forename: Tom
authors.initials: T
authors.lastname: Lutalo
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Wawer
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.forename: Susan H
authors.initials: SH
authors.lastname: Eshleman
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006679:HIV Seropositivity / Q000453:epidemiology / Q000378:metabolism*; D015497:HIV-1; D054884:Host-Pathogen Interactions; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D014454:Uganda / Q000453:epidemiology
chemical_list: D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4