LSU DENTAL COBRE: ORAL PAPILOMAVIRUS IN THE HIV CO-INFECTED HOST

人类免疫缺陷病毒（HIV）已经感染了全世界超过3400万人，并且这种感染导致免疫抑制，选择性地耗尽CD4 + T细胞。这种免疫功能的降低导致许多口腔感染，超过50%的HIV感染者发展出涉及口腔的病理学。在引起口腔疾病的病原体中，粘膜萎缩性人乳头状瘤病毒（HPV）是最常见的病毒性性传播疾病，也是粘膜疣和肛门生殖器恶性肿瘤的病原体。HPV相关的口腔病变包括尖锐湿疣、局灶性上皮增生和一些鳞状细胞癌。由HPV引起的口腔和生殖器病变在合并感染HIV的人中更常见。通过高效抗逆转录病毒治疗（HAART），HIV +患者的全身免疫重建已经完成，导致死亡率、发病率以及全身和口腔机会性感染降低，包括HPV诱导的宫颈病变消退。巧合的是，最近的报道已经注意到在HAART存在下与HPV感染一致的口腔病理学的增加。如果这一观察结果能够得到证实，它表明宿主对口腔HPV感染的防御与HAART恢复的防御无关，并且可能受到不利影响。不幸的是， 了解HIV阳性患者的HPV感染自然史或局部免疫系统 功能障碍，允许HPV口腔病变的发展。我们假设口腔HPV感染和疾病是由于HIV合并感染个体的口腔免疫力下降所致，这种免疫力不能恢复，并可能通过HAART进一步降低。为了开始检验这一假设，我们将研究有效的HAART治疗对HPV感染进展的影响，以及对病毒的唾液免疫应答，然后是发展HPV相关口腔病变的局部免疫应答的特征。本研究的结果将评估在治疗口腔HPV感染中可能的免疫潜力。

Human immunodeficiency virus (HIV) has infected over 34 million people worldwide and this infection leads to immune suppression with selective depletion of CD4 + T cells. This decrease in immune function leads to numerous oppommistic infections with over 50% of HIV-infected individuals developing pathology involving the oral cavity. Among the pathogens responsible for oral disease is the mucosatropic human Papilloma virus (HPV), which is the most common viral sexually transmitted disease and the etiologic agent of mucosal warts and anogenital malignancies. HPV associated oral lesions include condyloma, focal epithelial hyperplasia and some squamous cell carcinomas. Both oral and genital lesions caused by HPV are more commonly seen in those co-infected with HIV. Systemic immune reconstitution for the HIV + patient has been accomplished with highly active anti-retroviral therapy (HAART) leading to decreases in mortality, morbidity as well as systemic and oral opportunistic infections, including regression of HPV-induced cervical lesions. Paradoxically, recent reports have noticed increases in oral pathology consistent with HPV infection in the presence of HAART. If this observation can be confirmed, it suggests that the host defense against oral HPV infection is independent of that restored by HAART and may be adversely affected. Unfortunately, little is known about the natural history of HPV infection in the HIV-positive patient or the local immune dysfunction allowing the development of HPV oral lesions. We hypothesize that oral HPV infection and disease results from decreased oral-based immunity in the HIV co-infected individual that cannot be restored and is potentially reduced further by HAART. To begin to test this hypothesis, we will investigate the impact of effective HAART therapy on the progression of HPV infection and also the salivary immune response to the virus, followed by the characterization of the local immune response in those that develop HPV-related oral lesions. Results from this study will be evaluated for possible immunotherapeutic potential in the treatment of oral HPV infections.