HIV AND EBV INTERACTION IN ORAL MUCOSAL EPITHELIUM

人类免疫缺陷病毒（HIV）的口腔传播作为艾滋病毒/艾滋病传播的潜在危险因素正在得到深入研究，但艾滋病毒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，两者均可检测到HIV，表明口腔在HIV传播和传播中发挥着关键作用。体外的初级口腔角质形成细胞也可被HIV-1感染，并且它们可将病毒转移至淋巴细胞。我们的初步数据表明，HIV-1转胞吞作用可以穿过极化的底特律咽上皮细胞，这表明口腔HIV传播可能是通过上皮屏障的跨上皮转胞吞作用发生的，而不感染上皮细胞。我们还发现，与 HIV/AIDS 相关的口腔病变（称为毛状白斑）中的上皮间朗格汉斯细胞 (LC) 同时感染 HIV 和 EBV，这表明 LC 和 HIV-EBV 发挥着关键作用 HIV口腔发病机制中的相互作用。由于适用于体内和体外口腔粘膜 目前还没有用于评估 HIV 感染的上皮模型系统，我们在本提案中的目标是建立口腔粘膜组织的体外器官培养系统，并用它来研究 HIV-1 感染。该系统还将用于研究 HIV 和 EBV 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）建立口腔鳞状组织来源的体外器官培养模型。 (2)研究器官性口腔粘膜上皮细胞培养物中HIV-1的感染情况。 (3)研究EBV对器官性口腔粘膜上皮组织模型朗格汉斯细胞HIV感染的影响。这些研究结果将为口腔粘膜上皮HIV感染机制以及口腔上皮间LC中HIV-EBV感染在HIV发病机制中的作用提供新的详细信息。

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.