Borggren Marie, Jansson Marianne
Virus Research and Development Laboratory, Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen, Denmark.
Department of Laboratory Medicine, Lund University, Lund, Sweden; Department of Microbiology, Tumor and Cell biology, Karolinska Institute, Stockholm, Sweden.
Prog Mol Biol Transl Sci. 2015;129:109-40. doi: 10.1016/bs.pmbts.2014.10.004. Epub 2014 Dec 1.
The phenotype of human immunodeficiency virus type 1 (HIV-1) commonly evolves between and within infected individuals, at virus transmission, and during disease progression. This evolution includes altered interactions between the virus and its coreceptors, i.e., chemokine receptors, as well as mannose C-type lectin receptors (CLRs). Transmitted/founder viruses are predominantly restricted to CCR5, whereas the subsequent intrapatient evolution of HIV-1 coreceptor use during progressive disease can be subdivided into two distinct pathways. Accordingly, the CCR5-restricted virus population is either gradually replaced by virus variants able to use CXCR4 or evolves toward an altered, more flexible use of CCR5. Despite a strong dependency on these coreceptors for host cell entry, HIV-1 also interacts with other cell surface molecules during target cell attachment, including the CLRs. The virus interaction with the CLRs may result either in the efficient transfer of virus to CD4(+) T cells or in the degradation of the virus in endosomal compartments. The determinants of the diverse outcomes depend on which CLR is engaged and also on the glycan makeup of the envelope glycoproteins, which may evolve with the strength of the immune pressure during the disease course. With the current clinical introduction of CCR5 antagonists and the development of additional entry inhibitors, knowledge on the evolution and baseline characteristics of HIV-1 interactions with coreceptor and CLR interactions may play important roles for individualized and optimized treatment strategies. This review summarizes our current understanding of the evolution of HIV-1 interactions with these receptors.
1型人类免疫缺陷病毒（HIV-1）的表型通常在受感染个体之间、个体内部、病毒传播过程以及疾病进展期间发生演变。这种演变包括病毒与其共受体（即趋化因子受体）以及甘露糖C型凝集素受体（CLR）之间相互作用的改变。传播/奠基病毒主要局限于CCR5，而在疾病进展过程中HIV-1共受体使用的后续患者体内演变可分为两条不同的途径。因此，受CCR5限制的病毒群体要么逐渐被能够使用CXCR4的病毒变体所取代，要么朝着对CCR5的改变、更灵活的使用方向演变。尽管HIV-1进入宿主细胞强烈依赖于这些共受体，但在靶细胞附着过程中，HIV-1也会与其他细胞表面分子相互作用，包括CLR。病毒与CLR的相互作用可能导致病毒有效地转移到CD4(+) T细胞，也可能导致病毒在内体区室中降解。不同结果的决定因素取决于参与的CLR以及包膜糖蛋白的聚糖组成，后者可能会随着疾病过程中免疫压力的强度而演变。随着目前CCR5拮抗剂在临床上的应用以及其他进入抑制剂的开发，关于HIV-1与共受体相互作用以及CLR相互作用的演变和基线特征的知识可能对个体化和优化治疗策略发挥重要作用。本综述总结了我们目前对HIV-1与这些受体相互作用演变的理解。
