Impact of HERV-K expression on HIV-1 life cycle

HERV-K 表达对 HIV-1 生命周期的影响

• 批准号: 9037680
• 负责人: LUBBERTUS C MULDER
• 金额: $ 32.21万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9037680
• 关键词: Affect; Biological; CD4 Positive T Lymphocytes; Cells; Code; Complement; Complex; Computers; Custom; Data; Endogenous Retroviruses; Generations; Goals; HIV; HIV Infections; HIV-1; Health; Human; Human Genome; Individual; Infection; Knowledge; Lentivirus Infections; Life Cycle Stages; Lymphocyte; Malignant Neoplasms; Measures; Molecular; Molecular Profiling; Molecular Virology; Nature; Outcome; Pathogenesis; Patients; Physiological; Predisposition; Property; Proteins; Proviruses; RNA; Reporting; Resolution; Retroviridae; SIV; Scientist; Series; Shapes; Specificity; Staging; Structural Genes; Technology; Testing; Transcript; Tropism; Viral; Viral Physiology; Virion; Virulence; Virus; base; cell type; co-infection; deep sequencing; env Gene Products; gag Gene Products; insight; macrophage; novel; novel therapeutic intervention; protein K; research study; single molecule; stem; virus host interaction

DESCRIPTION: Eight percent of the human genome is of retroviral origin. Human endogenous retroviruses (HERV-K) RNA, proteins and virions have been detected in patients with cancer and HIV-1. There is abundant evidence that the expression of many endogenous retroviruses is up-regulated upon HIV-1 infection. Thus, HIV-1 infection in human cells is equivalent to a co-infection of several retroviruses. Because of the negative selection HERVs are subjected to, most of those endogenous retroviruses have lost their ability to replicate. We hypothesize that the interactions between endogenous retroviruses and HIV affect the outcome of exogenous the lentivirus infection and replication. Although there are at least 89 HERV-Ks in the human genome often they are studied as single provirus. Our objective is to delineate the full array of HERV-K transcripts present in primary cells prior as well as after infection with HIV, and determine how these co-infections change cellular and viral properties such as target cell susceptibility, viral infectivity and cell tropism. We propose to combine state-of-the-art deep sequencing technologies with molecular virology approaches to study HIV/HERV-K interactions at the molecular level. This approach will deliver: HERV-K expression profiling in primary cells in both infect and non-infected settings as well as the establishment of the impact that the relevant HERV-Ks have on the early late stages of the HIV life cycle.

描述：8%的人类基因组来自逆转录病毒。人类内源性逆转录病毒(HERV-K)RNA、蛋白质和病毒粒子已在癌症患者和HIV-1患者中检测到。大量证据表明，许多内源性逆转录病毒在HIV-1感染后表达上调。因此，HIV-1在人类细胞中的感染相当于几种逆转录病毒的混合感染。由于HERV的负选择，大多数内源性逆转录病毒已经失去了复制能力。我们假设内源性逆转录病毒和HIV之间的相互作用影响外源性慢病毒感染和复制的结果。虽然在人类基因组中至少存在HERV-K，但通常将它们作为单个前病毒进行研究。我们的目标是描绘在感染HIV之前和之后存在于原代细胞中的HERV-K转录本的完整阵列，并确定这些联合感染如何改变细胞和病毒的属性，如靶细胞易感性、病毒感染性和细胞嗜性。我们建议将最先进的深度测序技术与分子病毒学方法相结合，在分子水平上研究HIV/Herv-K的相互作用。这种方法将提供：HERV-K在原代细胞中的表达谱 包括感染和非感染环境，以及确定相关的HERV-K对艾滋病毒生命周期的早期和后期阶段的影响。