Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Curr HIV/AIDS Rep. 2012 Mar;9(1):52-63. doi: 10.1007/s11904-011-0107-3.
HIV-1 is completely dependent upon the Env protein to enter cells. The virus typically replicates in activated CD4+ T cells due to viral entry requirements for the CCR5 coreceptor and for high surface levels of the CD4 receptor. This is the case for the transmitted virus and for most of the virus sampled in the blood. Over the course of infection, the env gene can evolve to encode a protein with altered receptor and coreceptor usage allowing the virus to enter alternative host cells. In about 50% of HIV-1 infections, the viral population undergoes coreceptor switching, usually late in disease, allowing the virus to use CXCR4 to enter a different subset of CD4+ T cells. Neurocognitive disorders occur in about 10% of infections, also usually late in disease, but caused (ultimately) by viral replication in the brain either in CD4+ T cells or macrophage and/or microglia. Expanded host range is significantly intertwined with pathogenesis. Identification and characterization of such HIV-1 variants may be useful for early detection which would allow intervention to reduce viral pathogenesis in these alternative cell types.
HIV-1 完全依赖于 Env 蛋白进入细胞。由于病毒进入需要 CCR5 核心受体和高表面水平的 CD4 受体，因此该病毒通常在激活的 CD4+T 细胞中复制。这适用于传播的病毒和血液中大多数采样的病毒。在感染过程中，env 基因可能会进化为编码具有改变的受体和辅助受体使用的蛋白质，从而使病毒能够进入替代宿主细胞。在大约 50%的 HIV-1 感染中，病毒群经历辅助受体转换，通常在疾病晚期发生，使病毒能够利用 CXCR4 进入 CD4+T 细胞的不同亚群。大约 10%的感染会发生神经认知障碍，也通常在疾病晚期发生，但最终是由病毒在大脑中的 CD4+T 细胞或巨噬细胞和/或小胶质细胞中的复制引起的。宿主范围的扩大与发病机制密切相关。鉴定和表征此类 HIV-1 变体可能有助于早期检测，从而可以减少这些替代细胞类型中的病毒发病机制。
