DO TRANSCRIPTION ERRORS BY RNA POL II CONTRIBUTE TO VARIATION IN HIV

HIV-1是艾滋病的病原体，具有高度的基因组变异。的 高变异率使病毒能迅速进化出新的形式 它可以逃避宿主的免疫反应，并阻碍有效的免疫反应。 药物治疗和疫苗开发。三个不同的复制步骤 在病毒的生命周期中起作用：病毒逆转 转录酶（其将病毒基因组ssRNA转录成dsDNA）， 细胞DNA聚合酶（复制整合的前病毒），和 RNA pol II（再生病毒ssRNA）。艾滋病毒的一个来源 变异是病毒逆转录病毒DNA合成的低保真度 录酶人类复制保真度的测量 复杂性表明人类基因组的复制是高度精确的， 对艾滋病毒多样性贡献不大。然而， 与整合的病毒基因组是否被RNA转录有关， pol II产生病毒mRNA和基因组RNA，有助于HIV 变化量为了回答这个问题，我们发起了一个 研究RNA聚合酶的保真度，最终目标是 测量人RNA pol II复合物的保真度。我们目前正在 在此基础上发展了实验策略 用于通过HIV-1 RT测量逆转录的保真度。 实验策略，我们已经开始测量保真度 一个简单的转录系统，噬菌体T7的RNA聚合酶。

HIV-1, the causative agent of AIDS, exhibits high genomic variation. The high rate of variation permits rapid evolution of new forms of the virus that can evade the host immune response and hamper efforts for effective drug treatment and vaccine development. Three diferent replication steps operate during the life cycle of the virus: the viral reverse transcriptase (which transcribes the viral genomic ssRNA into dsDNA), cellular DNA polymerases (which replicate the integrated provirus), and RNA pol II (which regenerates the viral ssRNA). One source of HIV variation is the low fidelity of DNA synthesis by the viral reverse transcriptase. Measurements of the fidelity of the human replication complex indicate that replication of the human genome is highly accurate, contributing little to HIV diversity. However,there is little information bearing on whether transcription of the integrated viral genome by RNA pol II, to produce both viral mRNA and genomic RNA, contributes to HIV variation. In an attempt to answer this question we have initiated a study of the fidelity of RNA polymerases with the ultimate goal of measuring the fidelity of the human RNA pol II complex. We are currently developing the experimental strategy, which is addapted from the strategy for measuring the fidelity of reverse transcription by HIV-1 RT. To test the experimental strategy, we have initiated measurements of the fidelity of a simple transcription system, the RNA polymerase of bacteriophage T7.