Non-viral RNAs in HIV-1 particles

HIV-1 颗粒中的非病毒 RNA

基本信息

批准号：
7777806
负责人：
ALICE TELESNITSKY
金额：
$ 22.94万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-03-01 至 2012-02-28
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): RNA, but not necessarily the viral genome, is required for HIV-1 assembly, and roughly a third of the RNA in retroviral particles is host-encoded. The exquisite selectivity observed in some host RNAs' incorporation suggests specific molecular interactions are involved in their recruitment. However, the determinants and mechanisms governing incorporation of these host components into virions, and whether or not these RNAs affect virus properties, have remained largely unexplored. The proposed work examines the determinants of specific host RNAs' virion incorporation for both HIV-1 and the gammaretrovirus, MLV. This revised application includes preliminary data that solidify evidence for the active recruitment of some RNAs into retroviral particles and exclusion of other. The broad long term objectives are to advance general understanding of intracellular viral processes such as assembly, to determine which properties and molecular interactions dictate host small RNA packaging, and to address whether or not these small host RNAs affect retrovirus biology. Defining the molecular interactions necessary for the incorporation of these RNAs may increase the repertoire of potential antiretroviral targets. The specific aims are (1) to define the cis-acting determinants of 7SL RNA packaging and to explore whether host RNA-virus interactions appear direct or if they correlate with host protein recruitment (2) to exchange transcription signals to test the hypothesis that transcription by pol III predisposes an RNA for encapsidation and (3) to establish conditions that provide a selective advantage for 7SL RNA exclusion. PUBLIC HEALTH RELEVANCE: These studies will enhance understanding of highly conserved yet poorly understood components of viruses like HIV-1. Understanding how human RNA molecules are recruited into viruses may help clarify how progeny viruses form during infections, and may reveal new vulnerabilities that can be targeted in the development of new classes of antiviral drugs.

描述（由申请人提供）：HIV-1 组装需要 RNA，但不一定是病毒基因组，并且逆转录病毒颗粒中大约三分之一的 RNA 是宿主编码的。在一些宿主 RNA 的掺入中观察到的精确选择性表明，特定的分子相互作用参与了它们的募集。然而，控制这些宿主成分掺入病毒颗粒的决定因素和机制，以及这些 RNA 是否影响病毒特性，在很大程度上仍未得到探索。拟议的工作研究了 HIV-1 和伽马逆转录病毒 (MLV) 的特定宿主 RNA 病毒颗粒掺入的决定因素。该修订后的申请包括初步数据，这些数据巩固了一些 RNA 主动招募到逆转录病毒颗粒中并排除其他 RNA 的证据。广泛的长期目标是促进对细胞内病毒过程（例如组装）的一般理解，确定哪些特性和分子相互作用决定宿主小RNA包装，并解决这些小宿主RNA是否影响逆转录病毒生物学。定义这些 RNA 掺入所需的分子相互作用可能会增加潜在抗逆转录病毒靶标的库。具体目标是 (1) 定义 7SL RNA 包装的顺式作用决定因素，并探索宿主 RNA-病毒相互作用是否直接出现或是否与宿主蛋白招募相关 (2) 交换转录信号以检验转录的假设pol III 使 RNA 易于衣壳化，并且 (3) 建立为 7SL RNA 排除提供选择性优势的条件。公共卫生相关性：这些研究将增进对 HIV-1 等病毒高度保守但知之甚少的成分的了解。了解人类 RNA 分子如何被招募到病毒中可能有助于阐明子代病毒在感染过程中是如何形成的，并可能揭示可用于开发新型抗病毒药物的新漏洞。