HIV-1新重组株CRF55_01B的遗传变异及生物学特点研究

CRF55_01B是本团队2013年自我国男同性恋人群中鉴定的HIV-1新重组株，由CRF01_AE及B亚型HIV-1重组产生，近年来流行全国，在部分地区新诊断病例中占比10%以上。合作单位监测发现新诊断的CRF55_01B感染者，确诊基线时病毒载量及CD4+T细胞数“双高”，且CD4+T细胞数下降相对缓慢，与亲本毒株CRF01_AE及B亚型感染者不同，提示CRF55_01B毒株可能通过重组形成新的遗传及生物学特点。本研究拟以病毒单基因组扩增、下一代测序分析CRF55_01B毒株遗传进化特征；以Elispot法分析病毒对常见保护性细胞毒性T细胞应答的逃逸情况；以原代分离株、感染性克隆、env克隆及假病毒法研究病毒感染靶细胞的效率、辅助受体利用与转换、毒力、复制适应性、对宿主自体中和抗体反应性；揭示CRF55_01B毒株遗传变异与生物学表型的关系，为CRF55_01B感染防治提供科学依据。

CRF55_01B was identified as a novel circulating recombinant form of HIV-1 in 2013 by our team from men who have sex with men population in China, which has been prevalent throughout the country in recent years. In some areas, the infection caused by CRF55_01B among the new diagnosed HIV infected patients have represented over 10% of the total. A large sample monitoring study by our cooperators found that the newly diagnosed CRF55_01B infected people were characterized by "double high" on viral load and CD4+ T cell count at the time of HIV infection diagnosis, and the relatively slow decline of CD4+ T cell count at follow-up, which is distinct from the people infected with CRF01_AE and B subtype, the parent strains of CRF55_01B. It is suggested that CRF55_01B strain might have developed some new genetic variations and biological characteristics through the recombination event. This study aims to analyze the genetic variations on the genomes of CRF55_01B strains using single genome amplification, sanger sequencing and next-generation sequencing, to explore the adaptive evolution of CRF55_01B to the common protective cytotoxic T-cells responses with Elispot method, and to study the biological characteristics of CRF55_01B strains on the capacities of entry to the target cells, coreceptors usage and tropism shift, virulence, replication fitness and the reactivities to host autologous neutralizing antibodies using primary isolates, infectious clones, env clones and pseudovirus-based methods. This study will reveal the genetic variations and biological characteristics of CRF55_01B strains and the differences between CRF55_01B and its parent strains, CRF01_AE and subtype B, and provide scientific basis for the prevention and treatment of CRF55_01B infections.