Interaction of HIV envelope with cell surface receptors

HIV 包膜与细胞表面受体的相互作用

• 批准号: 8156927
• 负责人: Anthony S. Fauci
• 金额: $ 68.24万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8156927
• 关键词: Binding; CCR5 gene; CXCR4 gene; Cell Surface Receptors; Development; Disease; Exhibits; HIV; Lamina Propria; Process; Recombinants; env Gene Products; integrin beta7; prevent; transmission process; virus envelope; Binding; CCR5 gene; CXCR4 gene; Cell Surface Receptors; Development; Disease; Exhibits; HIV; Lamina Propria; Process; Recombinants; env Gene Products; integrin beta7; prevent; transmission process; virus envelope

The HIV envelope protein, gp120, mediates entry of viral particles into CD4+ T cells. This process requires that gp120 binds to both the CD4 receptor and a co-receptor, either CCR5 or CXCR4. Because gp120 is the only viral protein against which neutralizing antibodies are elicited, it is a key component of a potential AIDS vaccine. We have recently identified the integrin alpha4-beta7 as an additional HIV receptor on the surface of CD4+ T cells. The alpha4-beta7 receptor is the principal integrin involved in lymphocyte homing to the lamina propria of gut-associated lymphoid tissue (GALT), a site of considerable HIV replication especially during acute infection. Our observations suggest that the direct interaction between HIV gp120 and alpha4-beta7 provides a plausible mechanistic explanation for the preferential establishment and/or maintenance of HIV replication in GALT. Our current work is focused on the role of alpha4-beta7 integrin in HIV transmission. We are uncovering evidence indicating that transmitting viruses are specifically adapted to interact with alpha4-beta7 expressing CD4+ T cells. Under certain circumstances, we are finding that the envelope proteins of transmitting viruses interact differently with the CD4 receptor and alpha4-beta7 than do the envelopes of viruses replicating at later stages of disease. More specifically, our findings reveal that transmitting gp120s interact more efficiently with alpha4-beta7 and less efficiently with CD4 than other envelopes. In addition, the transmitting gp120s appear to exhibit unique structural properties that we have not yet fully characterized. These observations may provide important new information that will aid in the development of an effective vaccine to prevent HIV acquisition.

HIV包膜蛋白GP120介导病毒颗粒进入CD4+ T细胞。该过程要求GP120与CCR5或CXCR4的CD4受体和共受体结合。由于GP120是唯一引起中和抗体的病毒蛋白，因此它是潜在AIDS疫苗的关键组成部分。我们最近将整联蛋白α4-BETA7鉴定为CD4+ T细胞表面上的附加HIV受体。 Alpha4-Beta7受体是参与淋巴细胞归巢的主要整合蛋白，与肠道相关淋巴组织（GALT）的lamina lamina hous归，这是一个相当大的HIV复制部位，尤其是在急性感染期间。我们的观察结果表明，HIV GP120与Alpha4-Beta7之间的直接相互作用为GALT中HIV复制的优先建立和/或维持的合理机械解释提供了合理的机械解释。我们目前的工作集中在α4-Beta7整合素在HIV传播中的作用。我们正在发现证据表明，传播病毒是专门适用于与表达CD4+ T细胞的alpha4-beta7相互作用的。在某些情况下，我们发现传播病毒的包膜蛋白与CD4受体和α4-Beta7的相互作用与在疾病后期复制的病毒信封不同。更具体地说，我们的发现表明，与其他信封相比，传输GP120与Alpha4-Beta7的相互作用更有效，并且与CD4的效率更低。此外，传输GP120似乎表现出我们尚未完全表征的独特结构特性。这些观察结果可能会提供重要的新信息，这些信息将有助于开发有效的疫苗以防止艾滋病毒收购。