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：百分之八的人类基因组源自逆转录病毒。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和 HIV-1 患者中检测到。有大量证据表明，许多内源性逆转录病毒的表达在 HIV-1 感染后上调。因此，人类细胞中的HIV-1感染相当于几种逆转录病毒的共同感染。由于 HERV 受到负选择，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。尽管人类基因组中至少有 89 个 HERV-K，但它们通常被作为单一原病毒进行研究。我们的目标是描绘 HIV 感染之前和之后原代细胞中存在的完整 HERV-K 转录本，并确定这些共同感染如何改变细胞和病毒特性，例如靶细胞易感性、病毒感染性和细胞向性。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 相互作用。该方法将提供： 原代细胞中的 HERV-K 表达谱分析 感染和非感染环境以及相关 HERV-K 对 HIV 生命周期早期晚期阶段的影响的确定。