2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38013Human polyomavirus, JC virus, may cause a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML), of the central nervous system mostly in immunodeficiency patients. Moreover, JC virus may also be involved in human tumorigenesis. Most people are infected by the virus without clinical symptoms. The archetypal JC virus containing a single copy of the promoter and enhancer in the transcriptional control region was found in normal population. However, the rearranged JC virus containing deletions and/or duplications in the transcriptional control region was frequently found in PML patients. Therefore, it is speculated that different genotypes of the virus may correlate with replication activity. During past years, several genotypes, Taiwan-1 to Taiwan-12, of JC virus were isolated from patients with autoimmune diseases and renal transplantation in our laboratory. The purpose of this research proposal is to further investigate the biological activity of the different genotypes of JC virus. Transcription activity of the various genotypes will be analyzed using a luciferase reporter system in human brain cells. The cis and trans elements involved in JC virus gene regulation will be identified. In addition, expression of host transcriptional factors in different human cell lines will be analyzed to correlate viral pathology and tissue tropism.人類多瘤性病毒，JC 病毒，感染人類腦細胞後，可引發進行性多病灶腦白質症 （progressive multifocal leukoencephalopathy; PML）而導致病人死亡。此外，最近研究 發現JC 病毒可能與人類腦瘤之發生有關。雖然大多數人曾受JC 病毒感染，但只有少 數人因而發病。過去的研究發現，一般免疫正常的人體內大多存在原始型（archetype） JC 病毒，並且無明顯臨床症狀。然而，在進行性多病灶腦白質症病人體內所發現的JC 病毒大多為在起動子（promoter）重組（rearranged）的基因型。因此，目前推測起動 子之變異發生，可能與病毒複製活性及致病力有關。在過去幾年中，我們在台灣地區 從自體免疫病人及腎臟移植病人分離出多種基因型的JC 病毒。這些含有不同起動子的 JC 病毒，在病毒基因的轉譯活性及致病能力可能有所不同。在此研究中，我們將分析 不同起動子的JC 病毒，在病毒基因的轉譯活性。此外，參與該病毒基因調控之細胞因 子（host factors）及病毒起動子之cis elements 也將在計畫中加以鑑定。參與JC 病毒基 因調控之細胞因子可能有組織專一性（tissue specific），因而導致該病毒之組織偏好性 （tissue tropism）及致病性。此計畫也將探討這些細胞因子存在人類哪些細胞中。人類多瘤性病毒JC 病毒進行性多病灶腦白質症基因調控JC virusprogressive multifocal leukoencephalopathygene regulationProject