CHRONIC VIRAL INFECTIONS--MOLECULAR BIOLOGY OF HUMAN JC VIRUS

慢性病毒感染--人类JC病毒的分子生物学

• 批准号: 3922471
• 负责人: E O MAJOR
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3922471
• 关键词: B lymphocyte; DNA binding protein; Polyomavirus hominis 2; astrocytoma; chronic disease /disorder; gene expression; genetic mapping; genetic regulation; genetic transcription; glia; histopathology; human subject; molecular biology; nervous system disorder diagnosis; nervous system infection; nucleic acid hybridization; progressive multifocal leukoencephalopathy; tissue /cell culture; virus DNA; virus classification; virus diseases; virus genetics; virus infection mechanism

Progress has been made in the understanding of the pathogenesis of progressive multifocal leukoencephalopathy (PML), a subacute demyelinating disease resulting from infection of oligodendrocytes by JC virus (JCV). The use of DNA:DNA in situ hybridization has implicated JCV infection of mononuclear cells of the bone marrow and spleen as an important site for viral latency and probable spread of the virus to the brain. Immunocytochemical assays have identified the monoclear cells as B-lymphocytes. Furthermore, JCV infected monoclear cells were found in the Virchow-Robin spaces of the brain, which strongly suggests the involvement of lymphocytes in disease progression from systemic latency to a pathogenic state within the central nervous system (CNS). To account for the unique biological properties of JCV, an in-depth analysis of the viral genome within the regulatory region indicated an unusual DNA structure. S1 nuclease mapping and bromoacetaldehyde modification detected sensitive sites in the TATA box proximal to the origin of DNA replication. These results indicated the regulatory region contained non-B, but right handed DNA conformations, whose significance may reflect a role in the regulation of gene expression. The growing interest in developmental neurobiology and the availability of reagents has led to a study of the macroglial cells in human fetal brain cultures which support JC virus multiplication. Cellular compositions of short-term and cell suspension cultures of human brain from fetal ages 7 to 16 weeks were compared utilizing glial cell type-specific markers. In contrast to reports on the early rat CNS, human fetal glial cells characterized as Type II emerged developmentally before Type 1 glial cells. These results suggest fundamental differences in the chronology of development of phenotypically similar cells found in the rat and human nervous system.

的发病机制的认识已取得进展