HIV gp120来源的淀粉样纤维（GEVI）是申报人团队首次在国际上发现的存在于感染者的淋巴结，能显著促进HIV感染并拮抗抗病毒药物的药效，是HIV致病和病毒耐药潜在新机制。CD4+T淋巴细胞衰减是艾滋病发病的核心原因。近期我们发现GEVI自身能诱导CD4+T淋巴细胞的凋亡，并降低CD4+T淋巴细胞对胞外葡萄糖的摄取。糖代谢是细胞供能的主要途径。我们猜测GEVI沉积在细胞表面，模拟一种营养缺乏的环境，影响了细胞对糖的利用，诱导细胞凋亡。本研究拟研究GEVI诱导CD4+T淋巴细胞的毒性及凋亡机制；阐明此过程细胞糖代谢重编程的特点及相关信号通路，确证关键调控因子；同时也将评价GEVI对细胞膜的破坏作用；最后在大鼠模型上验证GEVI对CD4+T淋巴细胞的毒性作用。本研究以淋巴细胞糖代谢这一研究热点为切入点，把我们原创的GEVI在HIV致病机制中做更深入的探讨，预期为艾滋病的治疗提供新靶点。

HIV gp120 derived amyloid fibrils (GEVI) are first found in the lymph node of HIV infected patients by our group. GEVI displays potent ability to enhance HIV infection and antagonize the anti-viral activities of anti-retroviral drugs (ARVs). Therefore, GEVI might play a role in HIV pathogenesis and viral resistance to ARVs. The loss of CD4+ T cells leads to the AIDS. Recently, our results showed that GEVI could induce apoptosis of CD4+ T cells and CD4+ T cells had a lower uptake of extracellular glucose. Glucose metabolism is the main source of cellular energy. Our hypothesis is that, by coating on the cellular surface, GEVI influence the glucose uptake of CD4+ T cells, which leads to apoptosis. We intend to investigate the cytotoxicity effects of GEVI on CD4+ T cells and the apoptosis mechanism. We study the reprogrammed glucose metabolism and the involved signal pathway. We want to validate the key regulatory factor. As well, we evaluate the potential harmful effects of GEVI on cellular membrane. Finally, we confirm the cytotoxicity effects of GEVI on CD4+ T cells in the mouse model. Focus on the glucose metabolism of lymphocyte, this project aims to explore in depth the role of GEVI in HIV pathogenesis and provide a new target for anti-HIV therapy.