Host response to lentiviral infection

在慢病毒中，只有人类免疫缺陷病毒(HIV)和猫免疫缺陷病毒(FIV)利用无处不在的趋化因子和特定的T细胞受体的组合来进入病毒，并在其自然宿主中引起免疫缺陷。FIV与家猫和野猫共同进化的时间比HIV与人类进化的时间更长，与FIV感染相关的疾病在猫中的发展速度比艾滋病毒感染者的免疫缺陷更缓慢。此外，一些感染FIV的猫根本不会生病，而其他大多数猫最终会死于这种疾病。识别调节这种感染反应的猫宿主因素对于设计预防性或治疗性艾滋病毒干预措施非常有意义。因此，在这项研究中，我们将调查为什么一些猫由于感染FIV而出现NO或仅出现轻度免疫缺陷。首先，我们将通过对病毒蛋白及其修饰的分子检查来确定致病病毒和非致病病毒的构成差异。接下来，我们将研究这些不同的病毒如何改变树突状细胞(DC)的功能，树突状细胞是免疫反应的“主要”调节器。最后，我们将研究免疫系统，特别是辅助淋巴细胞和细胞毒性淋巴细胞如何对不同的病毒做出反应。这些研究将使我们深入了解，试图通过增加DC功能或减少免疫激活来操纵免疫缺陷病毒感染的早期阶段，是否可能改善感染的结果。此外，这些研究将阐明宿主免疫反应的性质和程度是否决定了免疫缺陷的发生，以及特定病毒的组成有多重要。

Among lentiviruses, only the human immunodeficiency virus (HIV) and the feline immunodeficiency virus (FIV) utilize a combination of ubiquitous chemokine and specific T-cell receptors for viral entry, and cause immunodeficiency in their natural hosts. FIV has co-evolved with domestic and wild cats for a longer time than HIV has with humans, and disease associated with FIV infection develops more gradually in cats than immunodeficiency in HIV-infected people. Further, some cats infected with FIV do not get ill at all, while most others eventually succumb to the disease. Identifying feline host factors that modulate this response to infection is of great interest for designing prophylactic or therapeutic HIV interventions. Therefore, in this research we will investigate why some cats develop either no or only mild immunodeficiency from infection with FIV. First, we will determine differences in the make-up of viruses that cause disease and those that don't cause disease by molecular examination of the viral proteins and their modifications. Next, we will examine how these different viruses alter the function of dendritic cells (DC), which are the "master" regulators of the immune response. Finally, we will investigate how the immune system, and specifically how helper and cytotoxic lymphocytes, respond to the different viruses. These studies will give us insight into whether trying to manipulate the early phase of immunodeficiency virus infection through increasing DC function, or reducing immune activation, may improve the outcome of infection. Further, these studies will clarify whether the nature and degree of the host immune response determines the onset of immunodeficiency, and how important the composition of the particular virus is.