OONO Takashi Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (80203884)
ASAGOE Kenji Okayama University, Hospital, Assistant Professor, 医学部・歯学部附属病院, 助手 (80294461)
|Budget Amount *help
¥11,800,000 (Direct Cost : ¥11,800,000)
Fiscal Year 2004 : ¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 2003 : ¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 2002 : ¥6,500,000 (Direct Cost : ¥6,500,000)
Latent EBV infection has been implicated in a variety of malignant conditions, including African Burkitt's lymphoma, nasopharyngeal carcinoma, post-transplantation lymphoproliferative disorders, natural killer (NK)/T-cell lymphomas, chronic active EBV infection, gastric cancer, pyothorax-associated lymphoma, and smooth-muscle tumors. Recently, patients in Asia, Mexico, and Peru with peculiar HV-like eruptions were found to progress to EBV-associated malignant lymphoma. Our study has clarified that both typical and severe HV are included within the spectrum of cutaneous disorders mediated by EBV-infected T cells, and the severe HV group may have overt EBV-associated NK/T cell lymphoproliferative disorders including hypersensitivity to mosquito bites, chronic active EB virus infection, hemophagocytic lymphohistiocytosis and NK/T cell lymphomas with a frequently fatal outcome. The development of and the progression to the severe HV-like lesions might occur endemically due to the influence
s of the patient's genetic background, EBV subtypes, immunological tolerance to EBV infection, or environmental factors.
Different T or NK cell lines infected with EB virus were established from the same patient, and different cell types were infiltrated in cutaneous lesions of hydroa vacciniforme and mosquito bites. These observations have demonstrated that the patients'blood contains a pool of EB virus-infected T, NK and B cells, which may explain a diversity of clinical symptoms related to latent EB virus infection. In the cutaneous lesions, we could find the involvement of cytotoxic T-cells and the clues of reactivation of EBV. A certain trigger such as mosquito bites and ultraviolet exposure may induce reactivation of EBV, which may in turn evoke secondary systemic symptoms.
In collaboration with Prof.S.Imai (Kochi Univ.), we have demonstrated that mutant EBNA1 can act as a dominant-negative effector that efficiently impedes the EBV-dependent malignant phenotypes in cells regardless of viral latency or tissue origin. This mutant will afford an additional therapeutic strategy specifically targeting EBV-associated malignancies.
For diagnostic purpose, we have established a real-time PCR method to determine the EBV DNA load, and a novel, noninvasive method to detect latent EBV infection in the skin crusts (PATENT : 2005-961917, Okayama Univ.). We believe that these technical advances contribute to the early diagnosis and the monitoring of the disease progression. Less