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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 C 亚型人类免疫缺陷病毒 1 型 (HIV-1) 占全球 HIV-1 新感染病例的 56% 以上，其中包括 HIV-1 从受感染妇女传播给其子女的情况。 HIV 的包膜糖蛋白通过受体相互作用定义细胞向性，并介导病毒与靶细胞的融合，在决定传播性方面发挥着主要作用。然而，在儿童 C 亚型的背景下，人们对环境进化、病毒适应性、传播和疾病进展之间的关系知之甚少。该假设认为，HIV-1 适应性与 Env 特性相关，并随着 Env 的变化而纵向进化，并且高适应性病毒优先从母亲传播到婴儿，在婴儿中它们介导更快的疾病进展。总体目标是确定病毒包膜在母婴传播和受感染儿童疾病进展中的作用，以及它与包膜序列变化的关系。我们之前纵向描述了赞比亚卢萨卡七名 C 亚型 HIV-1 围产期感染儿童的 HIV-1 包膜基因的进化，这些儿童具有不同的临床结果。我们创建了原病毒和 Env 表达构建体，其中包含源自 HIV-1 进化枝 B (NL4-3) 主链中这些母婴对的 C 亚型 Env 序列。我们现在利用所得嵌合体来测试Env加工、Env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，并确定与围产期传播或疾病进展相关的包膜的特定特征。这些被感染的孩子。