Journal
AIDS
Volume 19, Issue 10, Pages 1015-1024Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.aids.0000174447.48003.dd
Keywords
HIV-1; exposed seronegatives; genetic background; chromosome 22; neutralizing antibody; synteny; association study
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Objective: Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exposed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene. Methods: Based on our mapping in chromosome 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure. Results: A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups. Conclusions: The data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status. (c) 2005 Lippincott Williams & Wilkins.
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