VIROLOGIC CORRELATES OF HETEROSEXUAL TRANSMISSION

异性传播的病毒学相关性

• 批准号: 8357424
• 负责人: Eric Hunter
• 金额: $ 7.43万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357424
• 关键词: Antibodies; Biological; Blood; CD8-Positive T-Lymphocytes; Event; Female; Frequencies; Funding; Genetic Variation; Genital system; Grant; HIV; HIV Envelope Protein gp120; Heterosexuals; Immunoglobulins; Immunologics; Individual; Infection; Kinetics; Liquid substance; National Center for Research Resources; Population; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Rwanda; Screening procedure; Source; United States National Institutes of Health; Variant; Viral; Virus; Zambia; cost; genital secretion; superinfection; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objectives: To (1) determine whether sequence variants within gp120 are selected during transmission; (2) determine whether selection of viral variants reflects the population of virus present in the genital fluids of the donor or a biological restriction of the transmission process; (3) determine the frequency, kinetics, and the virologic and immunologic ramifications of HIV superinfection in both partners following early infection; and (4) to determine if uninfected partners sexually exposed to virus produce protective antibodies in their genital tract, thereby reducing opportunity for productive infection. Heterosexual HIV transmission is primarily a monophyletic event. To probe whether limited genetic diversity in the genital tract of the transmitting partner explains this bottleneck, viral envelope sequences from blood and genital fluids of 9 transmission pairs from Rwanda and Zambia were analyzed. The transmitting partner's viral population was heterogeneous with distinct stable genital sub-populations. Surprisingly, the transmitted founder variant was not derived from the predominant genital tract sub-populations. Hence, the transmission bottleneck is not driven by limited viral diversity in the genital tract, but instead involves selection of a more transmissible variant from the donor genital tract. Thus far, 4/44 individuals were also identified as being superinfected, but screening is costly and slow. 454 sequencing is now being used to enhance screening throughput. Genital secretions are being collected from seronegative exposed females and infected positive controls to determine whether local immunoglobulins in the genital tract protect against viral transmission and studies will also investigate whether protection involves CD8+ T lymphocytes.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 目标： (1) 确定 gp120 内的序列变体在传输过程中是否被选择； (2) 确定病毒变体的选择是否反映了供体生殖液中存在的病毒种群或传播过程的生物学限制； (3) 确定早期感染后伴侣双方 HIV 重复感染的频率、动力学以及病毒学和免疫学后果； (4) 确定性接触病毒的未感染伴侣是否在其生殖道中产生保护性抗体，从而减少生产性感染的机会。 HIV 异性传播主要是单系事件。为了探究传播伙伴生殖道中有限的遗传多样性是否解释了这一瓶颈，对来自卢旺达和赞比亚的 9 个传播对的血液和生殖液的病毒包膜序列进行了分析。传播伙伴的病毒种群是异质的，具有不同的稳定生殖器亚群。令人惊讶的是，传播的创始人变异并非源自主要生殖道亚群。因此，传播瓶颈并不是由生殖道中有限的病毒多样性驱动的，而是涉及从供体生殖道中选择更具传播性的变异体。到目前为止，4/44 人也被确定为重复感染，但筛查成本高昂且缓慢。 454 测序现在被用来提高筛选通量。正在从血清阴性暴露的女性和感染的阳性对照中收集生殖器分泌物，以确定生殖道中的局部免疫球蛋白是否可以防止病毒传播，研究还将调查保护是否涉及 CD8+ T 淋巴细胞。