The role of CCR5 and CCR2 polymorphisms in HIV-1 transmission and disease progression - PubMed (original) (raw)
The role of CCR5 and CCR2 polymorphisms in HIV-1 transmission and disease progression
N L Michael et al. Nat Med. 1997 Oct.
Abstract
Entry of human immunodeficiency virus type 1 (HIV-1) into target cells requires both CD4 (ref. 1, 2) and one of a growing number of G-protein-coupled seven-transmembrane receptors. Viruses predominantly use one, or occasionally both, of the major co-receptors CCR5 or CXCR4, although other receptors, including CCR2B and CCR3, function as minor co-receptors. CCR3 appears critical in central nervous system infection. A 32-base pair inactivating deletion in CCR5 (delta 32) common to Northern European populations has been associated with reduced, but not absolute, HIV-1 transmission risk and delayed disease progression. A more commonly distributed transition causing a valine to isoleucine switch in transmembrane domain I of CCR2B (64I) with unknown functional consequences was recently shown to delay disease progression but not reduce infection risk. Although we confirm the lack of association of CCR2B 64I with transmission, we cannot confirm the association with delayed progression. Although subjects with CCR5 delta 32 defects had significantly reduced median viral load at study entry, providing a plausible explanation for the association with delayed progression, this association was not seen with CCR2B 64I. Further studies are needed to define the role of CCR2B64I in HIV pathogenesis.
Comment in
- Wrong kind of chemokine research.
[No authors listed] [No authors listed] Nat Med. 1997 Oct;3(10):1051. doi: 10.1038/nm1097-1051a. Nat Med. 1997. PMID: 9334697 No abstract available. - CCR2 chemokine receptor and AIDS progression.
Smith MW, Carrington M, Winkler C, Lomb D, Dean M, Huttley G, O'Brien SJ. Smith MW, et al. Nat Med. 1997 Oct;3(10):1052-3. doi: 10.1038/nm1097-1052c. Nat Med. 1997. PMID: 9334699 No abstract available. - Genetic effects on HIV disease progression.
Ioannidis JP, O'Brien TR, Rosenberg PS, Contopoulos-Ioannidis DG, Goedert JJ. Ioannidis JP, et al. Nat Med. 1998 May;4(5):536. doi: 10.1038/nm0598-536. Nat Med. 1998. PMID: 9585207 No abstract available.
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