HIV AND EBV INTERACTION IN ORAL MUCOSAL EPITHELIUM

人类免疫缺陷病毒（HIV）的口腔传播作为HIV/艾滋病传播的潜在危险因素正在受到深入研究，但HIV与口腔粘膜上皮在体内相互作用的机制尚不清楚。对口咽粘膜上皮和唾液临床标本中HIV感染的分析表明，在两者中均可检测到HIV，表明口腔在HIV传播和传播中起关键作用。体外培养的原代口腔角质形成细胞也能被HIV-1感染，并能将病毒转移至淋巴细胞。我们的初步数据表明，HIV- 1转胞吞作用可以发生在极化的底特律咽上皮细胞，表明口腔HIV传播可能发生经上皮细胞转胞吞作用通过上皮屏障，而不感染上皮细胞。我们还发现，上皮间朗格汉斯细胞（LC）在艾滋病毒/艾滋病相关的口腔病变称为毛状白斑同时感染艾滋病毒和EBV，这表明LC和HIV-EBV的关键作用 口腔中HIV发病机制的相互作用。由于适用于体内和体外口腔粘膜 由于目前尚无评价HIV感染的上皮细胞模型系统，我们的目标是建立一种口腔粘膜组织体外器官培养系统，并利用该系统研究HIV-1感染。该系统还将用于研究HIV和EBV的相互作用，因为这两种病毒都可以在口咽粘膜上皮中复制。本研究的具体目的是：（1）建立口腔鳞状组织器官体外培养模型。(2)目的探讨HIV-1在口腔粘膜上皮细胞培养中的感染情况。(3)目的研究EB病毒对口腔粘膜上皮组织模型郎格罕细胞中HIV感染的影响。这些研究的结果将提供新的和详细的信息艾滋病毒感染的口腔粘膜上皮细胞的机制和艾滋病毒-EBV感染的作用，在口腔上皮间LC在艾滋病毒的发病机制。

Oral transmission of human immunodeficiency virus (HIV) as a potential risk factor for HIV/AIDS spread is being intensively investigated, but the mechanisms of HIV interaction with oral mucosal epithelium in vivo are not well understood. Analysis of HIV infection in clinical specimens of oropharyngeal mucosal epithelium and saliva showed that HIV can be detected in both, indicating a key role of the oral cavity in HIV transmission and dissemination. Primary oral keratinocytes in vitro also can be infected by HIV-1, and they can transfer virus to lymphocytes. Our preliminary data show that HIV- 1 transcytosis can occur across polarized Detroit pharyngeal epithelial cells, indicating that oral HIV transmission may occur by transepithelial transcytosis through the epithelial barrier without infecting the epithelial cells. We also found that interepithelial Langerhans cells (LCs) in the HIV/AIDS-associated oral lesion called hairy leukoplakia are infected simultaneously with HIV and EBV, suggesting a critical role of LCs and HIV-EBV interactions in HIV pathogenesis in the oral cavity. Since suitable in vivo and in vitro oral mucosal epithelial model systems for evaluation of HIV infection are not available, our goal in this proposal is to establish an in vitro organ culture system from oral mucosal tissue and to use it to investigate HIV-1 infection. This system will also be used to study HIV and EBV interaction, since both viruses can replicate in oropharyngeal mucosal epithelium. The specific aims of the study are: (1) To establish an in vitro organ culture model derived from squamous oral tissue. (2) To investigate infection of HIV-1 in the organotropic oral mucosal epithelial cell culture. (3) To study the effect of EBV on HIV infection in Langerhans cells of the organotropic oral mucosal epithelial tissue model. The results of these studies will provide new and detailed information on the mechanisms of HIV infection of the oral mucosal epithelium and the role of HIV-EBV infection in oral interepithelial LCs in HIV pathogenesis.