HIV AND EBV INTERACTION IN ORAL MUCOSAL EPITHELIUM

口腔粘膜上皮中 HIV 和 EBV 的相互作用

• 批准号: 6802946
• 负责人: SHAROF M TUGIZOV
• 金额: $ 22.73万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-15 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6802946
• 关键词: Epstein Barr virus; HIV infections; Langerhans' cell; biopsy; clinical research; communicable disease transmission; epithelium; flow cytometry; helper T lymphocyte; human immunodeficiency virus 1; human subject; immunofluorescence technique; mouth; oral mucosa; oral pharyngeal; organ culture; saliva; serum; technology /technique development; tissue /cell culture; tongue; transcytosis; virus virus interaction; western blottings

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.

人类免疫缺陷病毒(HIV)的口腔传播是HIV/AIDS传播的一个潜在危险因素，目前正被广泛研究，但HIV与口腔粘膜上皮在体内的相互作用机制尚不清楚。对临床标本口咽粘膜上皮和唾液中HIV感染的分析表明，两者都能检测到HIV，表明口腔在HIV传播和传播中起着关键作用。体外培养的原代口腔角质形成细胞也可以感染HIV-1，并将病毒传递给淋巴细胞。我们的初步数据显示，HIV-1可以通过极化的底特律咽上皮细胞发生跨细胞传递，这表明口腔传播可能是通过跨上皮跨细胞传递通过上皮屏障而不感染上皮细胞发生的。我们还发现，在HIV/AIDS相关的口腔病变中，称为毛状白斑的上皮间朗格汉斯细胞(LCS)与HIV和EBV同时感染，这表明LCS和HIV-EBV具有关键作用 口腔内HIV致病过程中的相互作用。适用于活体和体外口腔粘膜 目前尚无评估HIV感染的上皮模型系统，我们的目标是建立一种口腔黏膜组织的体外器官培养系统，并将其用于研究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细胞中复制。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)探讨HIV-1在口腔黏膜上皮细胞培养中的感染情况。(3)研究EB病毒对口腔黏膜上皮细胞感染HIV的影响。这些研究结果将为HIV感染口腔黏膜上皮的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。