Effects of HLA and KIR genotype on HIV and HCV

超出所提供的空间。本应用程序旨在研究人类白细胞抗原（HLA）和杀伤免疫球蛋白样受体（KIR）多态性对女性(i)感染HIV的风险，（ii）感染HCV的风险，以及（iii/iv） HIV和HCV感染过程的影响。HLA分子是多态蛋白，通过向t细胞提供抗原，在病毒免疫反应中发挥核心作用，并作为KIR（帮助调节自然杀伤细胞功能的多态分子）的配体。由于有共同的危险因素，艾滋病毒和丙型肝炎病毒影响相似的人群，合并感染很常见。对于HIV和HCV，以往的流行病学研究表明，HLA类型与感染过程有关。然而，已知的HLA和KIR的生物相互作用直到最近才被考虑到。我们小组在男性中进行的一项大型研究发现，HLA和KIR之间存在强烈的显著相互作用，与艾滋病毒/艾滋病的进展有关。HLA/KIR相互作用也在其他免疫相关疾病中被观察到。因此，了解HLA和KIR对于充分解释两者的数据是很重要的；在先前的HIV和HCV研究中数据不完整。迄今为止，尽管HIV自然史中存在性别差异，但女性的HLA数据却很少，令人惊讶的是，关于HLA等位基因对HAART的反应，甚至是感染HIV的风险，我们也知之甚少。我们对HCV和HLA型的了解更加不完整。HCV清除的研究几乎全部集中在HLA II类上，但在HCV的细胞毒性t细胞应答中起核心作用的是HLA Ia类。感染丙型肝炎病毒的风险从未被仔细研究过。计划中的研究将是第一个仔细评估HLA和KIR对女性HIV/AIDS进展、对HAART的反应、HIV感染风险、HCV病毒血症和HCV感染风险的独立作用和相互作用。为了解决这些问题，我们将在妇女机构间艾滋病毒研究（WIHS）中进行高分辨率HLA和KIR基因分型。WlHS是一个大的、种族和地理多样化的HIV(+) （n=2761, - 40% HCV(+)）和HIV（-）妇女的队列，她们具有相似的危险因素（n=942, - 25%HCV(+)）。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. This application is to study the effects of human leukocyte antigen (HLA) and killer immunoglobulin-like receptor (KIR) polymorphisms in women on (i) risk of infection by HIV, (ii) risk of infection by HCV, and (iii/iv) the course of HIV and HCV infections. HLA molecules are polymorphic proteins that play a central role in the immune response to viruses through the presentation of antigens to T-cells, and act as ligand for KIR (polymorphic molecules that help regulate natural killer cell function). Due to shared risk factors, HIV and HCV affect similar populations, and coinfection is common. For both HIV and HCV, previous epidemiologic studies have indicated that HLA type is related to course of infection. However, the known biologic interaction of HLA and KIR has only recently been taken into consideration. A large study in men conducted by our group found strong significant interactions between HLA and KIR associated with HIV/AIDS progression. HLA/KIR interactions have also been observed in other immune-related diseases. Thus, it is important to know both HLA and KIR to fully interpret the data for either; data that were incomplete in prior studies of HIV and HCV. Critical gaps in our knowledge regarding the effects of HLA type go substantially beyond the need to consider KIR, To date, there is a paucity of HLA data in women despite gender differences in HIV natural history and, surprisingly, little is also known regarding the HLA alleles associated with response to HAART, or even risk of becoming HIV infected. Our understanding of HCV and HLA type is even more incomplete. Studies of HCV clearance have focused almost entirely on HLA class II, but it is HLA class Ia that plays a central role in the cytotoxic T-cell response to HCV. Risk of becoming HCV infected has never been carefully studied. The planned study will be the first to carefully assess the independent effects and interactions of HLA and KIR on HIV/AIDS progression among women, response to HAART, risk of HIV infection, HCV viremia, and risk of HCV infection. To address these issues, we will conduct high resolution HLA and KIR genotyping in the Women's Interagency HIV Study (WIHS). WlHS is a large, racially and geographically diverse cohort of HIV(+) (n=2761 with - 40% HCV(+)), and HIV(-) women who share similar risk factors (n=942 with - 25%HCV(+)). PERFORMANCE SITE ========================================Section End===========================================