ROLE OF MONOCYTES IN AIDS AND AS TARGETS FOR ANTIVIRAL THERAPY

尽管在口腔中存在HIV-1， 病毒通过唾液传播尚未得到证实。 口腔传播的罕见性 尽管通过原位检测可识别HIV-1， 超过30%的艾滋病患者唾液腺中存在杂交 患者和艾滋病毒-1的口腔分泌物中的示范，涉及一个关键 先天抗病毒活性在抑制传播中的作用。 一个这样 内源性抗病毒分子，分泌性白细胞蛋白酶抑制剂 （SLPI），抑制HIV-1感染的单核细胞期间或之后不久 内化 进一步阐明SLPI在先天宿主中的功能 国防部，正在努力产生小鼠纯合子为零 SLPI突变。 在其他研究中，重点关注艾滋病毒的调节， 感染后的生产，条件致病菌被证明， 影响病毒复制。 通过原位杂交， 在合并感染的组织中检测到艾滋病毒水平。 引人注目 HIV-1 RNA信号的浓度在卡氏肺孢子虫或 鸟分枝杆菌感染淋巴结，大多数HIV阳性细胞 表达的巨噬细胞特异性标志物。 抗酸微生物染色 与原位杂交一起揭示了HIV的共定位， 单核和多核Langhans细胞中的鸟分枝杆菌。 初步 有证据表明，异常的巨噬细胞细胞因子表达是一种潜在的 控制这种大规模病毒复制的机制，即使在近 没有CD 4+淋巴细胞。 这些关于动态的新观察 机会致病菌、巨噬细胞和高水平 的病毒复制表明，共同感染是艾滋病毒的一个推动力， 生产，巨噬细胞有助于血浆病毒血症， 特别是在艾滋病晚期。 重要的是，这些观察 表明OI治疗不仅可以减少机会性病原体， 还能降低病毒负荷。

Despite the presence of HIV-1 in the oral cavity, transmission of the virus through saliva has not been proven. The rarity of oral transmission of HIV-1 by saliva, despite identification of HIV-1 by in situ hybridization in more than 30% of the salivary glands evaluated from AIDS patients and demonstration of HIV-1 in oral secretions, implicates a key role for innate antiviral activity in suppressing transmission. One such endogenous antiviral molecule, secretory leukocyte protease inhibitor (SLPI), inhibits HIV-1 infection of mononuclear cells during or soon after internalization. To further clarify the function of SLPI in innate host defense, efforts are underway to generate mice homozygous for a null mutation of SLPI. In additional studies focusing on the regulation of HIV production after infection, opportunistic pathogens were shown to influence viral replication. By in situ hybridization, unprecedented levels of HIV were detected in co-infected tissues. Striking concentrations of HIV-1 RNA signal were evident within P.carinii or M.avium infected lymph nodes, and the majority of HIV-positive cells expressed macrophage-specific markers. Staining for acid fast organisms together with in situ hybridization revealed co-localization of HIV and M.avium in mononuclear and multinucleated Langhans' cells. Preliminary evidence favors aberrant macrophage cytokine expression as a potential mechanism controlling this massive viral replication, even in the near absence of CD4+ lymphocytes. These novel observations on the dynamic relationship between opportunistic pathogens, macrophages and high levels of viral replication suggest that co-infection is an impetus for HIV production, and that macrophages contribute to plasma viremia, particularly in late-stage HIV-disease. Importantly, these observations suggest that OI therapy may not only diminish the opportunistic pathogens, but also decrease viral burden.