The role of viral phenotype and CCR-5 gene defects in HIV-1 transmission and disease progression.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

The role of viral phenotype and CCR-5 gene defects in HIV-1 transmission and disease progression.

Nat Med. 1997 Mar;3(3):338-40. Unique Identifier : AIDSLINE MED/97208922
Michael NL; Chang G; Louie LG; Mascola JR; Dondero D; Birx DL; Sheppard HW; Division of Retrovirology, Walter Reed Army Institute of Research,; Rockville, Maryland, USA.

Abstract: Cellular entry of human immunodeficiency virus type 1 (HIV-1) requires binding to both CD4 (ref, 1, 2) and to one of the chemokine receptors recently discovered to act as coreceptors. Viruses that infect T-cell lines to form syncytia syncytium-inducing, SI) are frequently found in late-stage HIV disease and utilize the chemokine receptor CXCR-4; macrophage-tropic viruses are non-syncytium-inducing (NSI), found throughout disease and utilize CCR-5 (ref. 3-11). We postulated that CCR-5 gene defects might reduce infection risk in seronegative subjects and prolong AIDS-free survival in seropositive subjects with NSI but not SI virus. Homozygous delta ccr5/delta ccr5) and heterozygous (CCR5/delta ccr5) CCR-5 deletions (delta ccr5) were found in 7 (2.7%) and 51 (19.5%), respectively, of 261 seronegative subjects from the San Francisco Men's Health Study. CCR-5/delta ccr5 genotype was identified in 33 of 172 (19.2%) nonprogressors and 25 of 234 (10.7%) progressors from the seropositive arm of this cohort. The delta ccr5 allele conferred a significant protective effect against HIV-1 infection (P = 0.001) and a survival advantage against disease progression (P = 0.02). Although both progressing and nonprogressing CCR5/delta ccr5 subjects were identified, a distinct survival advantage was shown for those with NSI virus (P < 0.0001). Thus, the protective effect of delta ccr5 against disease progression is lost when the infecting virus uses CXCR-4 as a coreceptor.

Keywords: *CD4-Positive T-Lymphocytes/VIROLOGY *HIV Infections/VIROLOGY *HIV-1/GENETICS *Receptors, Cytokine/GENETICS *Receptors, HIV/GENETICS
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