Adaptation to promiscuous usage of chemokine receptors is not a prerequisite for human immunodeficiency virus type 1 disease progression.
Fifty percent of individuals infected with human immunodeficiency virus type 1 (HIV-1) progress to AIDS in the presence of only non-syncytium-inducing (NSI) variants. These rapidly replicating NSI isolates are associated with a high viral load. The question of whether disease progression in the absence of syncytium-inducing (SI) HIV-1 variants is associated with an expansion of the coreceptor repertoire of NSI HIV-1 variants was studied. Biological HIV-1 clones were isolated both early and late in infection from progressors and long-term survivors with wild-type or mutant CCR5 or CCR2b genotypes and analyzed for their capacity to use CCR1, CCR2b, CCR3, CCR5, and CXCR4 on U87 cells coexpressing CD4. All HIV-1 clones were restricted to the use of CCR5. Absent replication of all HIV-1 clones in peripheral blood mononuclear cells from a CCR5 Delta32 homozygous blood donor confirmed this result. These findings indicate that an expanded coreceptor repertoire of HIV-1 is not a prerequisite for a progressive clinical course of HIV-1 infection.
de Roda Husman
A M
AM
Department of Clinical Viro-Immunology, CLB, Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
van Rij
R P
RP
Blaak
H
H
Broersen
S
S
Schuitemaker
H
H
D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D018450:Disease Progression; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology*; D015497:HIV-1 / Q000235:genetics; D018451:Homosexuality, Male; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics* / Q000276:immunology*; D018121:Receptors, Cytokine / Q000235:genetics; D017741:Survivors; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014162:Transfection; D019562:Viral Load
C515300:CCR1 protein, human; C515334:CCR2 protein, human; C515350:CCR3 protein, human; D015704:CD4 Antigens; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine