Proteomic Response of Oral and Intestinal Epithelial Cells to HIV

最近的研究表明，在艾滋病毒感染的急性期，肠道上皮的破坏是 与全身免疫激活和肠道丢失有关，其次是全身CD4T细胞。这个 HIV破坏肠上皮细胞(LECs)的机制尚未确定，也不知道是否 HIV对肠道上皮细胞的影响是间接的、直接的或两者兼而有之。 据报道，上皮性HIV对人类口腔上皮细胞(HOECs)的渗透使用了体外研究 证明口腔上皮细胞对无细胞和细胞相关的HIV挑战很敏感。在……里面 相比之下，流行病学证据表明，通过口腔组织感染艾滋病毒-1 上皮细胞是一种罕见的事件；当然，与通过以下两种途径感染的风险相比 生殖器或直肠粘膜。鉴于不同组织粘膜对艾滋病毒感染的不同易感性， 了解上皮细胞在预防艾滋病毒感染中所起的作用是重要的。我们假设 口腔粘膜上皮与肠道上皮相比具有固有的特性，这有助于其 对HIV-1跨细胞感染和后续感染的抵抗力。 HIV血清阳性者口腔和肠上皮细胞蛋白质组的比较 主题尚未定义。除了潜在的上皮固有反应元件外，还可能引发 为了预防HIV-1，我们还必须考虑艾滋病毒受试者的细胞反应受损，这可能是 被丙型肝炎病毒(丙型肝炎病毒)等混合感染困扰，丙型肝炎病毒通常在药物滥用中发现 通过对HIV和HIV个体的HOEC进行2D-DGE评估，我们发现 HIV感染者和非感染者之间的差异蛋白质表达谱。了解 上皮细胞在HIV感染中的作用及其固有的差异易感性 因此，人们对来自不同解剖位置的组织很感兴趣。这项试点的具体目标和 1)比较人口腔上皮细胞(HOECs)和人口腔上皮细胞(HOECs)的蛋白质组学特征 来自HIV、HIV(在HAART上)、HIV*/丙型肝炎病毒(在HAART上)和丙型肝炎病毒*的肠上皮细胞 研究对象，以及2.)比较(HIV)HOECs和LECs与HIV体外激发后的蛋白质组学特征， 和阿片类药物。

Recent work has suggested that disruption of the intestinal epithelium in the acute phase of HIV infection is associated with systemic immune activation and loss of intestinal followed by systemic CD4+ T cells. The mechanism by which HIV disrupts intestinal epithelial cells (lECs) has not been determined, nor is it known if effects of HIV on the intestinal epithelium are indirect, direct, or both. Epithelial HIV penetration has been reported for human oral epithelial cells (HOECs) using in vitro studies to demonstrate that oral epithelial cells are susceptible to cell free and cell-associated HIV challenge. In contrast, epidemiological evidence indicates that exogenous infection with HIV-1 through oral tissue epithelium is an uncommon event; certainly when compared to the risks for infection through either the genital or rectal mucosa. Given the differential susceptibilities of various tissue mucosa to HIV infection, understanding the role the epithelium plays in protection against HIV infection is important. We hypothesize that oral mucosal epithelium compared to intestinal epithelium has inherent properties that contribute to its resistance to HIV-1 transcytosis and subsequent infection. The proteome of oral and intestinal epithelial cells in HIV-seropositive subjects compared to uninfected subjects has not been defined. In addition to potential epithelial innate response elements that could elicit protection against HIV-1, we must also consider impaired cellular responses in HIV+ subjects that can be confounded by co-infections such as hepatitis C virus (HCV), commonly found in drug abusive HIV4" individuals. Using 2D-DIGE assessment of HOECs from HIV+ and HIV individuals, we identified differential protein expression profiles between HIV-infected and non-infected individuals. Understanding the role that the epithelium plays in HIV infection and inherent differential susceptibility properties of epithelial tissues derived from various anatomic locations is therefore of interest. The specific aims of this pilot and feasibility study are to: 1.)Compare proteomic profiles of human oral epithelial cells (HOECs) and intestinal epithelial cells (lECs) from HIV, HIV+(on HAART), HIV*/HCV+(on HAART) and HCV* subjects, and 2.) Compare proteomic profiles of (HIV) HOECs and lECs challenged in vitro with HIV, and opioids.