HIV-1与卡波氏肉瘤病毒（KSHV）共感染导致AIDS相关的卡波氏肉瘤（AIDS-KS）频繁发生。AIDS-KS预后差、治疗困难、往往在两年内死亡。我们前期的研究发现，HIV-1 Tat能够调控KSHV潜伏感染（J Virol，2007），增强KSHV Kaposin A和vIL-6致瘤（Neoplasia，2009；Oncogene，2013）。与Tat类似的HIV另一个可分泌、且易被体内多种细胞所摄取的蛋白- - Nef，是否有可能通过某种机制来调控KSHV另一致瘤蛋白K1诱导血管和肿瘤形成，从而参与AIDS-KS的发生？ 本研究的目的是证实Nef能够促进KSHV K1诱导血管生成和肿瘤形成；鉴定调控上述促进过程的关键信号通路；寻找调控上述促进过程的重要miRNAs，并阐明其作用机制。 研究结果有助于阐明AIDS-KS发病机理，为AIDS-KS治疗提供潜在的分子靶点。

Co-infection of Kaposi's sarcoma-associated herpesvirus (KSHV) and human immunodeficiency virus type 1 (HIV-1) induces the frequent occurrence of AIDS-related Kaposi's sarcoma (AIDS-KS). AIDS-KS patients with poor prognosis and treatment difficulties usually die in two years after infection. We have previously showed that HIV-1 Tat regulated KSHV latency (J Virol，2007) and enhanced KSHV Kaposin A and vIL-6-induced tumorigenesis (Neoplasia，2009；Oncogene，2013；PLoS One，2013). Therefore, the working hypothesis of this project is that， similar to Tat, Nef, an early and secreted protein of HIV-1, can promote KSHV oncoprotein K1-mediated angiogenesis and tumorigenesis by some mechanisms. To test this hypothesis, we will perform the following specific aims: (1) To confirm that HIV-1 Nef can facilitate KSHV K1-induced angiogenesis and tumorigenesis; (2) To identify the key signaling pathways and important miRNAs, which regulate HIV-1 Nef to promote K1-induced angiogenesis and tumorigenesis. This study will help to further understand the interaction between HIV-1 and KSHV, to clarify the molecular mechanism of AIDS-KS pathogenesis, and provide the theoretical basis for the treatment of AIDS-KS from the perspective of signal pathway and miRNAs.