Cohen O J, Kinter A, Fauci A S
National Institute of Allergy and Infectious Diseases, Laboratory of Immunoregulation, Bethesda, Maryland, USA.
Immunol Rev. 1997 Oct;159:31-48. doi: 10.1111/j.1600-065x.1997.tb01005.x.
Host factors play an important role in determining rates of disease progression in human immunodeficiency virus (HIV)-infected individuals. HIV is able to subvert the host immune system by infecting CD4+ T cells that normally orchestrate immune responses and by inducing the secretion of proinflammatory cytokines that the virus can utilize to its own replicative advantage. The recognition that certain chemokine receptors serve as necessary co-factors for HIV entry into its target cells as well as the fact that ligands for these receptors can modulate the efficiency of HIV infection has expanded the number and scope of host factors that may impact the pathogenesis of HIV disease. This area of investigation will no doubt yield novel therapeutic strategies for intervention in HIV disease; however, caution is warranted in light of the enormous complexity of the pleiotropic cytokine and chemokine networks and the uncertainty inherent in manipulating these systems. HIV-infected long-term non-progressors represent an excellent model to study potential host factors involved in HIV disease pathogenesis. Genetic factors certainly have a major impact on the immune responses mounted by the host. In this regard, a polymorphism in the gene for the HIV co-receptor CC chemokine receptor 5 (CCR5), which serves as a co-receptor for macrophage (M)-tropic strains of HIV, affords a high degree of protection against HIV infection in individuals homozygous for the genetic defect and some degree of protection against disease progression in HIV-infected heterozygotes. HIV-specific immune responses, including cytotoxic T-lymphocyte (CTL) responses and neutralizing antibody responses, also appear to play salutary roles in protecting against disease progression.
宿主因素在决定人类免疫缺陷病毒（HIV）感染个体的疾病进展速度方面起着重要作用。HIV能够通过感染通常协调免疫反应的CD4 + T细胞以及诱导促炎细胞因子的分泌来颠覆宿主免疫系统，而病毒可利用这些促炎细胞因子获得自身复制优势。认识到某些趋化因子受体作为HIV进入其靶细胞的必要辅助因子，以及这些受体的配体可以调节HIV感染效率，这使得可能影响HIV疾病发病机制的宿主因素的数量和范围有所扩大。这一研究领域无疑将产生干预HIV疾病的新治疗策略；然而，鉴于多效性细胞因子和趋化因子网络的巨大复杂性以及操纵这些系统所固有的不确定性，仍需谨慎。HIV感染的长期不进展者是研究参与HIV疾病发病机制的潜在宿主因素的极佳模型。遗传因素肯定对宿主产生的免疫反应有重大影响。在这方面，HIV共受体CC趋化因子受体5（CCR5）基因的多态性为该基因缺陷的纯合个体提供了高度的抗HIV感染保护，并为HIV感染的杂合子提供了一定程度的抗疾病进展保护，CCR5作为HIV巨噬细胞（M）嗜性毒株的共受体。HIV特异性免疫反应，包括细胞毒性T淋巴细胞（CTL）反应和中和抗体反应，在预防疾病进展方面似乎也起着有益作用。
