Role of Monocytes in AIDS and as Targets for Antiviral Therapy

该项目的研究旨在了解HIV-1感染的机制，特别是在巨噬细胞中，并制定有效的预防和/或抑制感染的策略。 HIV-1感染的后果是免疫缺陷，使宿主易于机会性感染。 反过来，机会性感染影响靶细胞对HIV-1感染和复制的易感性。利用M.作为模型共病原体，我们定义了多种病毒允许因子。此外，扁桃体和非感染性粘膜炎性病变中发生的免疫激活也可能与病毒复制的近端位点相关。 这些激活/炎症和增强HIV-1感染之间的联系保证了进一步阐明促进对HIV-1的宽容的因素。扁桃体代表了一个独特的微环境，拥有大量活化和高度敏感的HIV靶标。通过用HIV分离和培养扁桃体细胞，与不太敏感的外周血单核细胞相比，可以建立增强的易感性的表型、功能和分子相关性，并提供对干预靶点的了解。粘膜表面也是母乳喂养期间母婴HIV传播的一个位点，并且努力旨在定义传播动力学以及影响病毒传播的先天和获得性宿主防御机制的表达。内源性抗病毒分子，包括分泌性白细胞蛋白酶抑制剂（SLPI）和血小板反应蛋白（TSP-1），这对HIV-1感染的单核细胞具有抑制作用，发现在初乳中，然后下降，这表明一个潜在的增强防御的间隔。

Research in this project is directed at understanding the mechanisms of HIV-1 infection, particularly in macrophages, and in developing an effective strategy to prevent and/or inhibit infection. Immunodeficiency, the consequence of HIV-1 infection, predisposes the host to opportunistic infections. In turn, opportunistic infections influence target cell susceptibility to HIV-1 infection and replication. Using M. avium as a model co-pathogen, we have defined multiple viral permissive factors. Moreover, immune activation as occurs in tonsils and non-infectious mucosal inflammatory lesions may also be associated with proximal sites of viral replication. These connections between activation/inflammation and enhancement of HIV-1 infection warrant further elucidation of the factors promoting permissiveness to HIV-1. The tonsil represents an unique microenvironment possessing a large reservoir of activated and highly susceptible HIV targets. By isolating and culturing tonsil cells with HIV, phenotypic, functional and molecular correlates of enhanced susceptibility, as compared to less sensitive peripheral blood mononuclear cells, can be established and provide insight into interventional targets. The mucosal surface is also a site of maternal-to-child HIV transmission during breastfeeding and efforts are directed at defining the kinetics of transmission and the expression of innate and acquired host defense mechanisms which impact on viral transmission. Endogenous antiviral molecules, including secretory leukocyte protease inhibitor (SLPI) and thrombospondin (TSP-1), which have inhibitory actions on HIV-1 infection of mononuclear cells, are found in colostrum and then decline suggesting a potential interval of enhanced defense.