Viral and cellular factors affecting early steps in HIV reverse transcription

HIV生命周期中的关键事件之一是病毒RNA转化为双链DNA中间体。这个过程称为逆转录，是由病毒逆转录酶（RT）与其他病毒和细胞因子共同进行的。虽然HIV逆转录酶已被广泛研究，逆转录酶抑制剂已被用于HIV患者的抗逆转录病毒治疗，但其他对HIV有效逆转录至关重要的病毒和细胞因子尚未得到适当研究，可能代表一类新的抗HIV靶点>。目的是鉴定特别参与HIV逆转录早期步骤的病毒和细胞因子。我们已经获得了初步数据，这些数据导致了关于可能参与的病毒和细胞因子及其可能的作用模式的假设。实验已经被设计来专门证明或反驳这些假设。因此，该项目将帮助我们更全面地了解艾滋病毒如何使用其他病毒和细胞因子，除了RT，以完成其生长的强制性阶段之一（逆转录）;并确定可以进一步探索的病毒和细胞因子作为抗逆转录病毒治疗的新靶点。这一点特别重要，因为艾滋病毒对目前药物治疗的耐药性已成为艾滋病毒患者和艾滋病毒护理社区面临的一个严重问题。

One of the key events in the life cycle of HIV is the conversion of viral RNA into a double stranded DNA intermediate. This process, called reverse transcription, is carried out by the viral enzyme reverse transcriptase (RT) in conjunction with other viral and cellular factors. While HIV RT has been extensively studied and RT inhibitors have been used in anti-retroviral therapy for HIV patients, other viral and cellular factors essential for efficient HIV reverse transcription have not been properly investigated and may represent a new class of anti-HIV targets.This project, based on our long standing (>10 years) research interest and experience, aims at identification of the viral and cellular factors particularly involved in the early steps of HIV reverse transcription.We have obtained preliminary data which lead to hypotheses regarding what kind of viral and cellular factors might be involved and their possible modes of action. Experiments have been designed to specifically prove or disprove these hypotheses. Thus this project will help us achieve a more comprehensive understanding on how HIV uses other viral and cellular factors, in addition to RT, to accomplish one of the mandatory stage of its growth (reverse transcription); and identify viral and cellular factors which can be further explored as new targets for anti-retroviral therapy. This is particularly important, as HIV resistance to current drug therapy has emerged as one serious issue facing HIV patients, and the HIV care communities.