中缅边境新HIV-1重组型CRF83_cpx传播和流行的进化生物学研究

China-Myanmar border region is the hot spot of inter-subtype recombination of human immunodeficiency virus (HIV). Dozens of HIV circulating recombinant forms (CRF) had been identified in this region, but all with low prevalence. Our previous study identified a new HIV CRF in the Kokang Autonomous Region of Shan State in Myanmar, which named CRF83_cpx, with a prevalence of 42.3%. Our recent study also revealed that CRF83_cpx was epidemic in Yunnan of China. As CRF83_cpx had become the predominant strain in China-Myanmar border region, which had a complex subtype-circulating circumstance, we wonder whether it had a stronger virulence than other strains or not. To find this out, a cross-sectional survey will be conducted among newly reported HIV/AIDS patients in Yunnan border region, and the epidemic status of CRF83_cpx in this region will be determined. Further, wild infectious clones of CRF83_cpx and CRF01_AE will be constructed, as well as the pol/env gene replacement mutated infectious clones of CRF83_cpx and CRF01_AE. The influence of pol/env gene in the virulence of CRF83_cpx will be explored by comparing the amplification and infection capacity of these infectious clones, to reveal the possible evolution mechanism of CRF83_cpx in its expansion. The results of this study will provide some reference for the further understanding of the relationship between mutation and virulence, as well as the prevention of HIV/AIDS in Yunnan Province and other regions of China.

中缅边境是人类免疫缺陷病毒（HIV）亚型间重组的高发地区，近几年有十余种HIV流行重组型（CRF）在该地区被发现，但流行比例均较低。我们前期在缅甸果敢特区发现并命名的CRF83_cpx，流行比例高达42.3%。预实验证实，CRF83_cpx已出现在中国云南省。CRF83_cpx能在复杂重组毒株共流行的中缅边境呈现流行扩散的趋势，其病毒毒力可能与其它毒株存在差异。为了验证该假说，本项目拟对云南省边境地区新报告的HIV/AIDS感染者进行流行病调查，明确CRF83_cpx在该地区的流行现状。同时构建野生型以及pol或env基因相互置换的突变型CRF83_cpx和CRF01_AE感染性克隆，研究CRF83_cpx pol和env基因对病毒感染和复制能力的影响，揭示CRF83_cpx流行扩散可能的进化机制，为深入理解病毒变异与毒力之间的关系提供基础，为云南省及我国HIV/AIDS的防控提供参考。

中缅边境是人类免疫缺陷病毒1型（HIV-1）亚型间重组的高发地区，近几年有十余种HIV-1流行重组型（CRF）在该地区被发现，但流行比例均较低。项目组前期在缅甸果敢特区发现并命名的CRF83_cpx，流行比例高达42.3%。为了掌握CRF83_cpx在云南省境内的流行现状，探究其传播和流行的分子机制，项目组收集了云南省保山市和德宏州HIV-1新发感染者的血浆样本，扩增HIV-1 pol基因片段或HIV-1近全长基因组进行系统进化分析、重组分析、系统地理学分析。分子流行病学研究结果显示，虽然HIV-1 CRF83_cpx已经是缅甸北部克钦邦的优势流行株，但其在中国云南省的流行比例仍处于较低水平（1.4%）。进一步研究发现，中国云南省境内的HIV-1 CRF83_cpx起源于缅甸北部，且可能是由旅居云南省的缅甸籍人员携带而来。HIV-1 CRF83_cpx不仅正在扩散流行，而且参与了HIV-1新的独特重组型的重组过程，加速了中缅边境地区HIV-1的遗传复杂性。以上研究结果较为系统地阐明了中缅边境地区HIV-1 CRF83_cpx的流行现状，探究了其跨区域传播的动态过程和病毒进化的分子机制，为深入理解HIV-1新流行重组型的扩散流行提供基础，并为云南省及我国其他地区HIV-1/AIDS防控策略的制定提供科学参考。