LONGITUDINAL ANALYSIS OF HIV-1 CLADE C FITNESS

HIV-1 C 类适应性的纵向分析

• 批准号: 7719946
• 负责人: HONG ZHANG
• 金额: $ 17.06万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7719946
• 关键词: Accounting; Cells; Cellular Tropism; Characteristics; Child; Chimera organism; Clinical; Computer Retrieval of Information on Scientific Projects Database; Disease Progression; Evolution; Funding; Genes; Glycoproteins; Grant; HIV; HIV-1; Infant; Infection; Institution; Kinetics; Mediating; Mothers; Outcome; Perinatal; Play; Process; Property; Research; Research Personnel; Resources; Role; Source; Testing; United States National Institutes of Health; Vertebral column; Vertical Disease Transmission; Viral; Virus; Woman; Zambia; fitness; particle; receptor; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Subtype C human immunodeficiency virus type 1 (HIV-1) accounts for over 56% of HIV-1 new infections globally, including the transmission of HIV-1 from infected women to their children. The envelope glycoprotein of HIV plays the primary role in determining transmissibility by defining cellular tropism through receptor interactions, and by mediating fusion of virus to target cells. Yet very little is known about the relationships between Env evolution, viral fitness, transmission, and disease progression, in the context of subtype C in children. The hypothesis is that HIV-1 fitness correlates with Env properties and evolves longitudinally with changes in the Env, and that high fitness viruses are preferentially transmitted from mothers to infants where they mediate more rapid disease progression. The overall objective is to determine the role of viral envelope in mother to child transmission and disease progression in the infected children, and how it relates to changes in the Env sequences. We have previously longitudinally characterized the evolution of the HIV-1 envelope gene from seven subtype C HIV-1 perinatally infected children with different clinical outcomes from Lusaka, Zambia. We have created proviral and Env expression constructs containing subtype C Env sequences derived from these mother-infant pairs in an HIV-1 clade B (NL4-3) backbone. We have now utilized the resulting chimeras to test Env processing, Env mediated fusion, incorporation into viral particles, viral replication kinetics, neutralization sensitivity and replication capacity/fitness and determined the particular characteristics of the envelope that are correlated with perinatal transmission or disease progression in these infected children.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 亚型C人类免疫缺陷病毒1型（HIV-1）占全球HIV-1新感染的56％以上，包括将HIV-1从感染妇女传播到其子女。 HIV的包膜糖蛋白通过通过受体相互作用来定义细胞向tropism，以及通过介导病毒与靶细胞的融合来确定传播性的主要作用。然而，在儿童亚型C的背景下，Env进化，病毒适应性，传播和疾病进展之间的关系知之甚少。假设是HIV-1适应性与ENV的特性相关，并随着ENV的变化而纵向演变，并且高健身病毒优先从母亲传播到婴儿，在这些婴儿中介导了更快的疾病进展。总体目的是确定病毒包膜在母亲传播和疾病进展中的作用，以及它与ENV序列中的变化的关系。我们以前已经纵向表征了来自七个亚型C HIV-1围产期感染儿童的HIV-1包膜基因的演变，该儿童与赞比亚卢萨卡有不同的临床结果。我们创建了源自HIV-1进化枝B（NL4-3）主链中这些母伴对的亚型C ENV序列的病毒和ENV表达构建体。现在，我们利用所得的嵌合体来测试ENV加工，介导的融合，掺入病毒颗粒，病毒复制动力学，中和敏感性和复制能力/适应性，并确定了这些感染儿童中与周围传播或疾病相关的特定特征。