Role of CCR2 genotype in the clinical course of syncytium-inducing (SI) or non-SI human immunodeficiency virus type 1 infection and in the time to conversion to SI virus variants.
The effect of a valine to isoleucine switch in the CCR2 first transmembrane domain (CCR2 64I) on the clinical course of human immunodeficiency virus type 1 (HIV-1) infection was analyzed in relation to the presence or absence of syncytium-inducing (SI) HIV-1 variants. Compared with persons with a wild-type genotype for CCR2 and CCR5, subjects with a CCR2-64I/+ or 64I/64I (but CCR5 wild-type homozygous genotype) had significantly delayed disease progression (relative hazard, 0.66; 95% confidence interval, 0.44-0.99) with a 1. 5-fold slower CD4 T lymphocyte decline and a 1.2-fold lower RNA virus load. The delay in disease progression was more pronounced when only non-SI (NSI) HIV-1 variants were present and was not observed after conversion to SI HIV-1 in CCR2-64I/+ persons. In CCR2-64I/+ subjects, a higher conversion rate to and a higher prevalence of SI HIV-1 was observed. These findings suggest that the mechanism of action of the CCR2 polymorphism is mediated via CCR5-restricted NSI HIV-1 variants.
van Rij
R P
RP
Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands, Amsterdam, The Netherlands.
de Roda Husman
A M
AM
Brouwer
M
M
Goudsmit
J
J
Coutinho
R A
RA
Schuitemaker
H
H
D002478:Cells, Cultured; D016001:Confidence Intervals; D018450:Disease Progression; D014644:Genetic Variation; D005838:Genotype; D015726:Giant Cells; D006679:HIV Seropositivity / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D018451:Homosexuality, Male; D006801:Humans; D007532:Isoleucine; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008297:Male; D017354:Point Mutation; D016016:Proportional Hazards Models; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics*; D018121:Receptors, Cytokine / Q000235:genetics*; D013997:Time Factors; D014633:Valine
C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D007532:Isoleucine; D014633:Valine