van Rij R P, de Roda Husman A M, Brouwer M, Goudsmit J, Coutinho R A, Schuitemaker H
Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands, Amsterdam, The Netherlands.
J Infect Dis. 1998 Dec;178(6):1806-11. doi: 10.1086/314522.
The effect of a valine to isoleucine switch in the CCR2 first transmembrane domain (CCR2 64I) on the clinical course of human immunodeficiency virus type 1 (HIV-1) infection was analyzed in relation to the presence or absence of syncytium-inducing (SI) HIV-1 variants. Compared with persons with a wild-type genotype for CCR2 and CCR5, subjects with a CCR2-64I/+ or 64I/64I (but CCR5 wild-type homozygous genotype) had significantly delayed disease progression (relative hazard, 0.66; 95% confidence interval, 0.44-0.99) with a 1. 5-fold slower CD4 T lymphocyte decline and a 1.2-fold lower RNA virus load. The delay in disease progression was more pronounced when only non-SI (NSI) HIV-1 variants were present and was not observed after conversion to SI HIV-1 in CCR2-64I/+ persons. In CCR2-64I/+ subjects, a higher conversion rate to and a higher prevalence of SI HIV-1 was observed. These findings suggest that the mechanism of action of the CCR2 polymorphism is mediated via CCR5-restricted NSI HIV-1 variants.
分析了CCR2第一跨膜结构域中缬氨酸至异亮氨酸的转换（CCR2 64I）对1型人类免疫缺陷病毒（HIV-1）感染临床病程的影响，并与合胞体诱导（SI）HIV-1变异体的存在与否相关。与CCR2和CCR5野生型基因型的人相比，CCR2-64I/+或64I/64I（但CCR5野生型纯合基因型）的受试者疾病进展明显延迟（相对风险，0.66；95%置信区间，0.44 - 0.99），CD4 T淋巴细胞下降速度慢1.5倍，RNA病毒载量低1.2倍。当仅存在非SI（NSI）HIV-1变异体时，疾病进展的延迟更为明显，而在CCR2-64I/+的人中转换为SI HIV-1后未观察到这种延迟。在CCR2-64I/+受试者中，观察到向SI HIV-1的转化率更高且SI HIV-1的患病率更高。这些发现表明，CCR2多态性的作用机制是通过CCR5限制的NSI HIV-1变异体介导的。
