ANTIBODY NEUTRALIZATION AND ESCAPE IN SUBTYPE C HIV-1

C 亚型 HIV-1 中的抗体中和和逃逸

• 批准号: 8357423
• 负责人: Cynthia Ann Derdeyn
• 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/8357423
• 关键词: Antibodies; Antibody Formation; Autologous; B-Lymphocyte Subsets; B-Lymphocytes; Biology; Cercocebus atys; Chronic; Collaborations; Disease Progression; Failure; Funding; Glycoproteins; Grant; HIV Envelope Protein gp120; HIV-1; Immune response; Immunoglobulins; Infection; Link; Mediating; National Center for Research Resources; Primates; Principal Investigator; Production; Research; Research Infrastructure; Resources; Rwanda; SIV; Source; Staging; United States National Institutes of Health; Viral; Virus; Zambia; cost; human subject; immune activation; neutralizing antibody; response

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. Neutralizing antibodies in HIV-1 infection are directed against the envelope (Env) glycoproteins gp120 and gp41. However, HIV-1 Env utilizes highly effective, but poorly defined, mechanisms to evade antibody-mediated neutralization. The objective of these studies is to indentify the initial B cell targets and define mechanisms of viral escape in subjects that are newly infected with subtype A and C HIV-1 in Rwanda and Zambia, respectively. In year 03 of this R01, through collaboration with Dr. Guido Silvestri, we compared neutralizing antibody (Nab) responses against the autologous virus in HIV-1 infection vs. SIV infection of a natural host species, the sooty mangabey (Li et al). We demonstrated that high titer Nab develops in early HIV-1 infection and persists into the chronic stage of infection. However, SIV infection of sooty mangabeys does not elicit high titer Nab responses against the autologous virus. This finding suggests fundamental differences in the B cell response in pathogenic vs. nonpathogenic infection, and we are continuing to investigate the biology underlying this observation. We have demonstrated that B cells in chronic HIV-1 infection express increased levels of PD-1 and decreased levels of BTLA, compared to healthy human subjects (Boliar et al.). Expression of these markers was linked to increased immune activation throughout the B cells subsets and to the aberrant production of immunoglobulin. We are continuing to investigate how these abnormalities contribute to disease progression and failure of the humoral immune response in HIV-1 infection. FUNDING SOURCE: NIH

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。 HIV-1 感染中的中和抗体针对包膜 (Env) 糖蛋白 gp120 和 gp41。然而，HIV-1 Env 利用高效但定义不明确的机制来逃避抗体介导的中和。这些研究的目的是确定卢旺达和赞比亚分别新感染 A 型和 C 型 HIV-1 的受试者的初始 B 细胞靶标并确定病毒逃逸机制。 在本 R01 的第 03 年，通过与 Guido Silvestri 博士合作，我们比较了 HIV-1 感染中的自体病毒与天然宿主物种乌白眉白眉的 SIV 感染中对自体病毒的中和抗体 (Nab) 反应（Li 等人） 。我们证明，高滴度 Nab 在 HIV-1 感染早期形成，并持续到感染的慢性阶段。然而，乌白眉猴的 SIV 感染不会引发针对自体病毒的高滴度 Nab 反应。这一发现表明 B 细胞反应在致病性与非致病性感染中存在根本差异，我们正在继续研究这一观察结果背后的生物学原理。我们已经证明，与健康人类受试者相比，慢性 HIV-1 感染中的 B 细胞表达的 PD-1 水平升高，而 BTLA 水平降低（Boliar 等）。这些标记物的表达与整个 B 细胞亚群的免疫激活增加以及免疫球蛋白的异常产生有关。我们正在继续研究这些异常如何导致 HIV-1 感染中的疾病进展和体液免疫反应失败。 资金来源：美国国立卫生研究院