The influence of MT-2 tropism on the prognostic implications of the delta32 deletion in the CCR-5 gene.

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

The influence of MT-2 tropism on the prognostic implications of the delta32 deletion in the CCR-5 gene.

AIDS. 1997 Oct;11(12):1415-9. Unique Identifier : AIDSLINE /MED98000110
Bratt G; Sandstrom E; Albert J; Samson M; Wahren B; Gay Men's Health Clinic, the Department of Dermatovenereology,; Stockholm Soder Hospital, Sweden.

Abstract: BACKGROUND: Long-term non-progression in HIV-1-infected patients has been reported to be associated with a 32 base-pair deletion delta32) in one CCR-5 allele. The normal gene product acts as a coreceptor for HIV cell entry and is essential for infection of cells by non-syncytium-inducing and MT-2-negative HIV-1 strains. METHODS: Forty individuals were studied, all of whom had been HIV-1-seropositive for a mean of 8 years. RESULTS: Eight (20%) were heterozygous for the CCR-5 allele delta32 deletion. Six of these eight patients harboured MT-2-negative HIV-1 strains. Of these six, three were long-term non-progressors with a positive CD4 cell slope, not receiving antiretroviral treatment, whereas the other three were progressors (mean CD4 cell decline, 3.8 x 10(6)/l per month) receiving antiretroviral combination therapy. Two of the eight patients with the delta32 deletion had MT-2-positive HIV-1 strains. Both had very rapid CD4 cell decline 6.7 and 7.6 x 10(6)/l per month, respectively), despite triple antiretroviral therapy including a protease inhibitor. One of the patients with an MT-2-positive virus strain has suffered from Pneumocystis carinii bronchitis and the other from cytomegalovirus colitis. CONCLUSIONS: Disease progression may also occur in individuals with the coreceptor deficiency, especially in association with MT-2-positive HIV-1 strains. It is suggested that MT-2-positive HIV-1 enters cells through the CXC chemokine receptor-4 fusin coreceptor, thus circumventing the defective CC chemokine receptor-5 coreceptor. Various levels of expression of the wild-type CCR-5 gene and the gene with the delta32 deletion might explain variations in the disease progression in heterozygous patients with MT-2-negative HIV-1 strains.

Keywords: *Gene Deletion *HIV Infections/GENETICS *HIV-1 *Receptors, CCR5/GENETICS
980130
M9811078

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