Morawetz R A, Rizzardi G P, Glauser D, Rutschmann O, Hirschel B, Perrin L, Opravil M, Flepp M, von Overbeck J, Glauser M P, Ghezzi S, Vicenzi E, Poli G, Lazzarin A, Pantaleo G
Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Eur J Immunol. 1997 Dec;27(12):3223-7. doi: 10.1002/eji.1830271220.
Homozygous (delta ccr5/delta ccr5) and heterozygous (CCR5/delta ccr5) deletions in the beta-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/delta ccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts > 500/microl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/delta ccr5 genotype. However, when LTNP were analyzed separately, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69% of LTNP) and the heterozygous (31.0%) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/delta ccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/delta ccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.
β趋化因子受体5（CCR5）基因中的纯合子（δccr5/δccr5）和杂合子（CCR5/δccr5）缺失，分别与抵抗HIV感染和预防疾病进展有关，该基因编码嗜巨噬细胞HIV-1进入的主要共受体。与先前研究一致，发现CCR5/δccr5基因型在长期不进展者（LTNP）中出现的频率（31.0%）高于疾病进展者（10.6%，p<0.0001）。Kaplan-Meier生存分析表明，疾病进展较慢，即CD4+T细胞计数>500/微升的受试者比例较高（p=0.0006），以及向艾滋病进展较慢的趋势（p=0.077），与CCR5/δccr5基因型有关。然而，当单独分析LTNP时，在野生型（占LTNP的69%）和杂合子（31.0%）基因型之间，未观察到CD4+T细胞计数（p=0.12）和病毒血症水平（p=0.65）的显著差异。因此，在大多数LTNP中，还有其他因素在决定疾病不进展状态方面起主要作用。此外，没有证据表明CCR5/δccr5基因型与疾病进展组中不同的疾病进展率有关。综上所述，这些结果表明，CCR5/δccr5基因型对于预防HIV疾病进展既不是必需的，也不是充分的。
