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/AIDS传播的潜在危险因素正在被深入研究，但HIV与口腔黏膜上皮相互作用的体内机制尚不清楚。对临床标本口咽粘膜上皮和唾液中HIV感染情况进行分析，发现两者均可检出HIV，提示口腔在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被HIV-1感染，并可将病毒转移到淋巴细胞。我们的初步数据显示，HIV- 1胞吞作用可以发生在极化的底特律咽上皮细胞中，这表明HIV可能通过上皮胞吞作用穿过上皮屏障而发生口腔传播，而不感染上皮细胞。我们还发现，在与HIV/ aids相关的口腔病变（称为毛状白斑）中，上皮间朗格汉斯细胞（LCs）同时感染HIV和EBV，这表明LCs和HIV-EBV具有关键作用

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.