Role of Oral Epithelial Cells in HIV-1 Transmission

口腔上皮细胞在 HIV-1 传播中的作用

• 批准号: 6881405
• 负责人: Zina Moldoveanu
• 金额: $ 18.13万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-05 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6881405
• 关键词: CD4 molecule; HIV infections; biopsy; cell adhesion molecules; cell line; cellular immunity; cellular pathology; chemokine; chemokine receptor; clinical research; communicable disease transmission; cytoprotection; epithelium; gastric mucosa; gastrointestinal epithelium; genital secretion; human immunodeficiency virus 1; human subject; intestinal mucosa; mucosal immunity; mucus; oral mucosa; patient oriented research; polymerase chain reaction; receptor expression; rectum /anus; sample collection; semen; virus receptors

The first line of defense against HIV-1 infections and the primary site for their transmission are mucosal surfaces of the oral cavity and the genital, and gastrointestinal tracts. The rate of HIV-1 transmission through oral cavity is significantly lower than the transmission through the genital or intestinal routes, although it still carries a risk. To address the question of oral resistance or susceptibility to HIV-l-infection, this application focuses on the cellular factors that reduce the transmission rate in oral cavity. Specifically, we propose to: 1. Establish whether oral epithelia are less capable of transferring HIV-1 from infected lamina propria cells into oral secretions than the genital or rectal epithelia. To accomplish this aim, approximately 50, primarily HIV-1 infected adults, not taking ART medication will be enrolled and asked to donate saliva, intestinal, cervicovaginal or seminal fluids and peripheral blood. Differences occurring between the HIV-1 released in saliva vs. the genital or rectal secretions, will be determined in the same individual with respect to: a) levels of free and cell-associated virus; b) its capacity to generate a productive infection; c) phenotype(s) (X4 or R5) of infectious viruses, and type of cells containing HIV-I. 2. Determine whether the expression of HIV-1 receptors and co-receptors and of relevant adhesion molecules on oral epithelia causes them to be less effective than the genital or rectal epithelia in transferring HIV-lfrom the apical surface to the subepithelial target cells. Differences in CD4, GaI-Cer, CCR5, CXCR4, ICAM-2 and ICAM-3 expression and the distribution of HIV-1 target cells will be ascertained on explant tissues of oral, rectal and genital origin. Moreover, their potential of epithelia to selectively transport/be infected and generate a productive infection by HIV-1 phenotypes in free or cell-associated forms will be determined. Finally, by means of epithelial cell lines, it will be established whether the free HIV-1 receptors and co-receptors released from the oral epithelial cells can prevent the access of HIV-1 to its target cells. The data generated will contribute to the understanding of mucosal HIV-1 transmission.

抵抗HIV-1感染的第一道防线和主要传播部位是口腔、生殖器和胃肠道的粘膜表面。HIV-1通过口腔传播的比率明显低于通过生殖器或肠道传播的比率，尽管它仍然存在风险。为了解决口腔对hiv - 1感染的抗性或易感性问题，本应用程序侧重于降低口腔传播率的细胞因素。具体而言，我们建议：