JCV Virus Expression in Oropharynx and HIV

JCV 病毒在口咽部和 HIV 中的表达

• 批准号: 6656747
• 负责人: JOSEPH R BERGER
• 金额: $ 22.05万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6656747
• 关键词: HIV infections; Polyomavirus hominis 2; clinical research; communicable disease transmission; glia; helper T lymphocyte; human subject; immunosuppression; leukocyte activation /transformation; leukocyte count; oral pharyngeal; progressive multifocal leukoencephalopathy; saliva; secretion; virus DNA; virus infection mechanism; virus load

DESCRIPTION (provided by applicant): Serological studies indicate that more than 80% of the world's adult population is infected with JC virus, a papovavirus. The mode of transmission of this virus is unknown and acute infection has not been recognized as a cause of an identifiable illness. However, JCV is the cause of progressive multi focal leukoencephalopathy (PML), a formerly rare demyelinating disease of the brain. PML has become common in the face of the HIV pandemic affecting approximately 5% of all AIDS patients, usually during advanced stages of immunosuppression. JCV remains latent in the reticuloendothelial system following the initial infection. Demonstration of the virus in tonsillar tissue suggests an oropharyngeal or respiratory mode of transmission. JCV is also expressed periodically in peripheral blood lymphocytes (PBLs). These cells share regulatory regions for the virus with CNS glial cells infected in PML. While JCV can be identified in the PBLs of approximately 5% of otherwise normal individuals, it is demonstrable in the PBLs of approximately 50% of immunosuppressed individuals, including those with AIDS, and in 90% of persons with AIDS-associated PML. The expression of JCV in the oropharyngeal fluids has not been previously determined. We hypothesize that JCV is shed in oropharyngeal fluids and that its presence in these fluids will correlate with both its presence in PBLs and the severity of immunosuppression. The aims of this study include identifying JCV in saliva and throat washings in three populations (normal controls, HIV-infected persons, and persons with AIDS-associated PML); determining whether a correlation exists between JCV presence in oropharyngeal fluids and in PBLs; and determining whether JCV shedding from the oropharynx correlates with the degree of immunosuppression. This line of investigation would add credence to an oropharyngeal mechanism of JCV transmission and may ultimately lead to the clinical identification of an acute illness attributable to this pathogen.

描述（由申请人提供）：血清学研究表明，世界上80%以上的成年人感染了JC病毒，一种乳头状病毒。这种病毒的传播方式尚不清楚，急性感染尚未被确认为导致某种可识别疾病的原因。然而，JCV是进行性多灶性脑白质病（PML）的病因，PML是一种以前罕见的脑部脱髓鞘疾病。在艾滋病毒大流行的情况下，PML变得很常见，约占所有艾滋病患者的5%，通常发生在免疫抑制的晚期。初次感染后，JCV在网状内皮系统中仍然潜伏。在扁桃体组织中发现病毒表明是口咽或呼吸道传播方式。JCV也在外周血淋巴细胞（PBLs）中周期性表达。这些细胞与PML感染的中枢神经胶质细胞共享病毒的调控区域。虽然在大约5%的正常个体的PBLs中可以发现JCV，但在大约50%的免疫抑制个体（包括艾滋病患者）和90%的艾滋病相关PML患者的PBLs中可以发现JCV。JCV在口咽液中的表达此前尚未确定。我们假设JCV在口咽液中传播，并且其在这些液体中的存在将与其在pbl中的存在和免疫抑制的严重程度相关。本研究的目的包括在三个人群（正常对照组、hiv感染者和艾滋病相关PML患者）的唾液和咽洗液中鉴定JCV；确定口咽液中JCV的存在与pbl之间是否存在相关性；以及确定口咽部的JCV脱落是否与免疫抑制程度相关。这一调查路线将增加JCV口咽传播机制的可信度，并可能最终导致由该病原体引起的急性疾病的临床鉴定。