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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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，包括HIV-1从受感染妇女传播给其子女。HIV的包膜糖蛋白通过受体相互作用确定细胞向性，并介导病毒与靶细胞的融合，在确定传播性方面发挥主要作用。然而，在儿童C亚型的背景下，对Env进化、病毒适应性、传播和疾病进展之间的关系知之甚少。该假说是HIV-1适应性与Env特性相关，并随着Env的变化纵向进化，并且高适应性病毒优先从母亲传播给婴儿，在那里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感染儿童疾病进展中的作用，以及它与Env序列变化的关系。我们以前纵向特征的演变HIV-1包膜基因从7个亚型C HIV-1围产期感染的儿童不同的临床结果从卢萨卡，赞比亚。我们已经创建了前病毒和Env表达构建体，其含有在HIV-1进化枝B（NL 4 -3）骨架中衍生自这些母婴对的亚型C Env序列。我们现在已经利用得到的嵌合体来测试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，并确定与这些感染儿童中的围产期传播或疾病进展相关的包膜的特定特征。