THE ROLE OF CCR5 AND CCR2 POLYMORPHISMS IN HTV-1 TRANSMISSION AND DISEASE PROGRESSION

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 althou gh other receptors, including CCR2B and CCR3, function as minor co-rec eptors(4-6). CCR3 appears critical in central nervous system infection (7). A 32-base pair inactivating deletion in CCRS (Delta 32) common to Northern European populations(8) has been associated with reduced(9-1 5), but not absolute(16-19), HIV-1 transmission risk and delayed disea se progression(11-15,20). A more commonly distributed transition causi ng a valine to isoleucine switch in transmembrane domain I of CCR2B (6 41) with unknown functional consequences was recently shown to delay d isease progression but not reduce infection risk(21). Although we conf irm the lack of association of CCR2B 641 with transmission, we cannot confirm the association with delayed progression. Although subjects wi th CCRS Delta 32 defects had significantly reduced median viral load a t study entry, providing a plausible explanation for the association w ith delayed progression, this association was not seen with CCR2B 641. Further studies are needed to define the role of CCR2B 641 in HIV pat hogenesis.