ROLE OF MONOCYTES IN AIDS AND AS TARGETS FOR ANTIVIRAL THERAPY

尽管口腔中存在HIV-1，但通过唾液传播病毒的情况很少见，这意味着天生/自然的抗病毒机制可以抑制传播。这些内源性抗病毒分子，包括分泌性白细胞蛋白酶抑制物(SLPI)和凝血酶反应蛋白(TSP-1)，在内化过程中或之后不久抑制单个核细胞感染HIV-1。为了进一步阐明SLPI的抗病毒功能及其在天然宿主防御中的作用，多方面的研究表明，SLPI除了具有抗蛋白降解活性外，还可以抑制转录因子NF-kappa B，从而阻断单核/巨噬细胞细胞因子和趋化因子的合成。SLPI零突变纯合子小鼠的产生为其表达、功能和调控模式提供了洞察力。在关注感染后艾滋病毒产生的调节的其他研究中，机会病原体和免疫激活被证明影响病毒复制。例如，禽分枝杆菌通过激活核因子-kappa B途径来刺激细胞因子和趋化因子的产生以及艾滋病毒共受体(CCR5)的表达，同时抑制细胞凋亡，从而促进艾滋病毒感染。这会导致易感病毒宿主细胞的积累，这有利于病毒复制。在扁桃体和粘膜炎症部位，淋巴细胞、巨噬细胞和高水平艾滋病毒之间的动态关系强调了免疫激活有助于病毒的进展，并提出了干预方法。

Despite the presence of HIV-1 in the oral cavity, transmission of the virus through saliva is rare, which implicates innate/natural antiviral mechanisms for suppressing transmission. Such endogenous antiviral molecules, including secretory leukocyte protease inhibitor (SLPI) and thrombospondin (TSP-1) inhibit HIV-1 infection of mononuclear cells during or soon after internalization. To further clarify the antiviral functions of SLPI as well as its role in innate host defense, a multifaceted approach has revealed that in addition to antiproteolytic activity, SLPI inhibits the transcription factor NF-kappa B to block monocyte/macrophage cytokine and chemokine synthesis. Generation of mice homozygous for a null mutation of SLPI have provided insight into its patterns of expression, function and regulation. In additional studies focusing on the regulation of HIV production after infection, opportunistic pathogens and immune activation were shown to influence viral replication. For example, Mycobacterium avium promotes HIV infection by activating the NF-kappa B pathway to stimulate cytokine and chemokine production and HIV co-receptor (CCR5) expression, while inhibiting apoptosis. This results in accumulation of susceptible viral host cells which favors viral replication. In tonsils and in sites of mucosal inflammation, the dynamic relationship between lymphocytes, macrophages and high levels of HIV emphasizes that immune activation contributes to viral progression and suggests interventional approaches.