HIV-1的隐身术:变异与进化

The invisibility of HIV-1: variation and evolution

HIV-1以其庞大的基因多样性及快速的变异能力,不断地逃逸人类免疫系统的监控,至今为止,尚未研发出有效的疫苗和治愈方法。研究HIV-1的进化模式及其与人类免疫系统之间的"博弈",有助于鉴定新的抗病毒治疗靶点、探寻可诱导广谱免疫应答的免疫表位和设计新型有效的艾滋病疫苗。现从HIV-1进化的角度,简述了HIV-1的起源、分类、流行;讨论了HIV-1基因多样性产生的原因及其快速的进化模式;分析了HIV-1变异与中和抗体产生以及特异CTL作用之间的关联;总结了HIV-1在抗病毒药物治疗下的进化;最后也概括了HIV-1适应宿主限制性因子的作用,以期为艾滋病治愈策略及有效疫苗研发提供借鉴。

A series of challenges including enormous genetic diversity and rapid evolution, which enable HIV-1 to escape host immune surveillance, has hindered the development of the effectively protective vaccine and a functional cure strategy against HIV-1/AIDS. Exploring the relationship between HIV-1 evolution and human immune responses will help to develop effective HIV-1 vaccines to elicit broaden neutralizing responses and specific cross-reactive CTL responses, which can also help to identify new target for exploring HIV-1/AIDS cure strategy. From an evolutionary perspective, here, we summarized the study progress on origin, classification and epidemic of HIV-1, followed by the genetic diversity and rapid evolution model of HIV-1. In addition, we highlighted the relationship between variability of HIV-1 and the host adaptive immune responses, as well as the variability of HIV-1 under anti-retroviral therapy. The intrinsic host restriction factors were also depicted. We hope that this review will provide clues to design new vaccines and HIV-1/AIDS cure strategies.