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％的人基因组是逆转录病毒的起源。在癌症和HIV-1患者中，已经检测到人内源性逆转录病毒（HERV-K）RNA，蛋白质和病毒素。有大量证据表明，HIV-1感染后许多内源性逆转录病毒的表达被上调。因此，人类细胞中的HIV-1感染等同于几种逆转录病毒的共感染。由于选择了负面选择，因此大多数内源性逆转录病毒都失去了复制能力。我们假设内源性逆转录病毒与HIV之间的相互作用会影响慢病毒感染和复制的外源性结果。尽管人类基因组中至少有89个HERV-K，但它们被研究为单一病毒。我们的目标是描述先前和感染HIV后原代细胞中存在的全部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，例如靶细胞敏感性，病毒感染性和细胞感性。我们建议将最新的深层测序技术与分子病毒学方法相结合，以研究分子水平的HIV/HERV-K相互作用。这种方法将传递：HERV-K在原代细胞中的表达分析 感染和未感染的环境以及相关HERV-KS对HIV生命周期晚期的影响的建立。