Humoral response to viral and self-antigens in HIV infection

描述：如果病毒载量保持在最低水平，HIV阳性个体的疾病预后会显著改善。一些非进展者似乎具有在不存在抗病毒疗法的情况下控制病毒表达的先天能力，并且通常认为病毒血症的这种控制主要由对病毒的体液和/或细胞免疫应答决定。然而，非进展者和快速进展者都表现出对HIV的实质性免疫应答，其中体液抗体应答特别针对主要中和靶点，即病毒包膜。与FIV感染相关的体液抗体反应的研究表明，在高比例的感染猫中存在针对主要结合受体CD 134的抗体。此外，这些抗CD 134抗体在体外阻断FIV感染，并且它们的存在与体内低/慢疾病进展相关。与CD 134的反应性发生在仅在病毒结合时暴露的隐蔽表位处，从而避免潜在的自身免疫问题。本研究的目的是追求对HIV主要结合受体，CD 4，我们已经确定在筛选约300名HIV感染者的血清中的同源抗受体抗体的特性。我们希望确定疾病进展的速度/程度与抗CD 4抗体应答的产生之间是否存在关系;以及2）抗CD 4抗体的子集是否干扰HIV感染。为此，我们提出以下目标：（1）。使用免疫亲和法从患者血清中纯化抗CD 4抗体，并评估这些抗体对病毒摄取到靶细胞中的影响; 2）继续筛选其他患者血清，以评估抗CD 4、抗SU和抗Gag体液抗体应答作为疾病进展速率/程度的函数，通过相对CD 4+和CD 8 + T细胞水平和病毒载量进行测量。这些发现将增加我们对抗病毒反应性质的理解，因为它与保护有关，从而有助于开发更有效的疫苗策略。

DESCRIPTION: The disease prognosis for HIV positive individuals is markedly improved if viral loads are kept at a minimum. Some non-progressors appear to have an innate ability to control virus expression in the absence of antiviral therapies and it is generally assumed that this control of viremia is largely dictated by the humoral and/or cellular immune response to the virus. However, both non-progressors and rapid progressors exhibit substantial immune responses to HIV, with humoral antibody responses particularly directed at the major neutralization target, the viral envelope. Studies of the humoral antibody response associated with FIV infection has revealed the presence of antibodies to the primary binding receptor, CD134, in a high percentage of infected cats. Furthermore, these anti-CD134 antibodies blocked FIV infection ex vivo and their presence correlated with low/slow disease progression in vivo. Reactivity with CD134 occurs at a cryptic epitope that is only exposed when virus binds, thus avoiding potential autoimmune issues. The purpose of the present studies is to pursue characterization of the homologous anti-receptor antibodies against the HIV primary binding receptor, CD4 that we have identified in screening the sera of approximately 300 HIV-infected patients. We wish to determine whether there is a relationship between rate/extent of disease progression and generation of anti-CD4 antibody responses; and 2) whether a subset of anti-CD4 antibodies interfere with HIV infection. To this end, we propose the following Aims: 1). Use Immunoaffinity to purify anti-CD4 antibodies from patient serum and assess the influence of those antibodies on virus uptake into target cells; and 2) Continue screening of additional patient serum to assess anti-CD4,anti-SU, and anti-Gag humoral antibody responses as a function of rate/extent of disease progression, as measured by relative CD4+ and CD8+ T cell levels and viral load. The findings will increase our understanding of the nature of the antiviral response as it relates to protection and thus aid in development of more efficacious vaccine strategies.