UKY DENTAL COBRE: ORAL INFECTIONS AND HIV RECRUDESCENCE

2000年底，估计有3 600多万人感染了人体免疫机能丧失病毒。HAART疗法（高效抗逆转录病毒疗法）的引入显著改变了艾滋病毒疾病的病程，延长了艾滋病毒感染者的生存率，提高了生活质量。然而，用现有的抗逆转录病毒疗法无法完全根除艾滋病毒感染。这主要是由于在急性HIV感染的最早阶段建立了一个潜伏感染的CD 4 + T细胞库，并以极长的半衰期持续存在。HIV-1在静止的CD 4 + T细胞和巨噬细胞内的这种持续存在构成了控制HIV-1感染的主要障碍。目的是记录口腔微生物激活HIV的能力和变化（1），评估口腔微生物刺激宿主细胞释放激活HIV-1的介质的能力，并确定有助于这一过程的细胞受体。一般假设：慢性牙周炎相关的口腔微生物可以潜在地激活T细胞和/或巨噬细胞 感染了HIV-1，导致病毒复发。具体目的a：确定选定的口腔微生物激活潜伏感染的T淋巴细胞和巨噬细胞中HIV-1的能力。待检验的假设是：慢性牙周感染中包含口腔生物膜的选定口腔微生物将激活潜伏感染的T细胞和巨噬细胞中的HIV-1。我们将使用模型T细胞a巨噬细胞系（1G 5; BF 24，转染 与HIV启动子）和（J1.1; OM 10.1，HIV-1的再活化）。具体目标二：确定选定的口腔微生物从常驻细胞群中诱导介体的能力，这些介体可激活潜伏感染的T淋巴细胞和巨噬细胞中的HIV-1。待检验的假设是：由口腔微生物刺激的成纤维细胞和上皮细胞产生的介体将激活潜伏感染的T细胞和巨噬细胞中的HIV。具体目标3：确定潜伏感染的T细胞和巨噬细胞中细菌和宿主刺激HIV启动子和HIV再激活的靶受体。待检验的假设是：潜伏感染的T细胞和巨噬细胞上存在特异性受体，其将结合细菌或宿主配体，转导导致HIV活化的细胞内信号。慢性牙周炎是人类最普遍的感染的临床表现，尚未研究改变HIV感染中持续性病毒库的联系。记录慢性感染引发牙周炎的能力，也可以表现为细菌的外周易位，具有激活潜伏感染的T淋巴细胞和/或巨噬细胞的能力，这可能对理解HIV感染中的口腔系统疾病联系产生重大影响。口腔细菌病原体可能有助于这种细胞间信号传导的潜力也将有助于更清楚地了解HAART治疗的成功/失败，以及影响HIV储库的长期策略。牙周炎的预防和干预是非常具有成本效益的措施，因此，包括 将艾滋病毒感染者的基本健康改善/维持战略纳入其中可能会产生重大的公共卫生效益。

At the end of 2000 it was estimated that over 36 million people were living with the human immunodeficiency virus. The introduction of HAART regimens (Highly Active Antiretroviral Therapy) has significantly modified the course of HIV disease, with longer survival rates and improvement of life quality in HIV-infected individuals. However, complete eradication of HIV infection cannot be achieved with currently available antiretroviral regimens. This primarily results from the establishment of a pool of latently infected CD4+ T cells during the very earliest stages of acute HIV infection that persists with an extremely long half-life. This persistence of HIV-1 within resting CD4+ T cells and macrophages constitutes a major obstacle in the control of HIV-1 infection. The aims are developed to document the capacity and variation in the ability of oral microorganisms to activate HIV(1), to evaluate the ability of oral microorganisms to stimulate resident host cells releasing mediators that would activate HIV-1, and to determine cellular receptors that contribute to this process. The General Hypothesis is that: Oral microorganisms associated with chronic periodontal infections can activate T cells and/or macrophages latently infected with HIV-1, leading to viral recrudescence. Specific Aim a: To determine the capacity of selected oral microorganisms to activate HIV-1 in latently infected T lymphocytes and macrophages. The hypothesis to be tested is: Selected oral microorganisms comprising the oral biofilm in chronic periodontal infections will activate HIV-1 in latently infected T cells and macrophages. We will use model T cell a macrophage cell lines (1G5; BF24, transfected with the HIV promoter) and (J1.1; OM10.1, reactivation of HIV-1) in these studies. Specific Aim 2: To determine the ability of selected oral microorganisms to elicit mediators from resident cell populations that can activate HIV-1 in latently infected T lymphocytes and macrophages. The hypothesis to be tested is: Mediators produced by fibroblasts and epithelial cells stimulated with oral microorganisms will activate HIV in latently infected T cells and macrophages. Specific Aim 3: To determine the target receptors for bacterial and host stimulation of the HIV promoter and HIV reactivation in latently infected T cell and macrophages. The hypothesis to be tested is: There are specific receptors on the latently infected T cells and macrophages that will bind bacterial or host ligands, transducing an intracellular signal leading to activation of HIV. Chronic periodontitis, which represents the clinical presentation of the most ubiquitous infection of mankind, has not be examined for a link altering the persistant viral reservoir in HIV infection. The ability to document that the chronic infection triggering periodontitis, which can also be manifest by peripheral translocation of bacteria, has the capacity to activate latently infected T lymphocytes and/or macrophages could have a substantial impact on understanding oral-systemic disease linkages in HIV infection. The potential that the oral bacterial pathogens could contribute to this inter-cellular signaling would also add to a clearer insight into HAART therapy success/failure, as well as long-term strategies to impact HIV reservoirs. Prevention and intervention for periodontitis are very cost-effective measures, thus, including this strategy into the basic health improvement/maintenance of HIV-infected individuals could have significant public health benefits.