| Summary: | 碩士 === 慈濟大學 === 醫學生物技術研究所 === 96 === Clinical evidence suggests that hepatitis C virus (HCV) isetiologically involved in liver cirrhosis, hepatic cancer, and B-celllymphomas. In our previous study, HCV NS3 protease domain but not helicasedomain was found to interact with dNT-1, cytosolic 5'(3')-deoxyribonucleotidase,in yeast two hybrid system. dNTs are present in most mammaliancells and have been involved in the regulation of intracellular dNTP poolsby substrate cycles. Substrate cycles are relying on the interplay betweena deoxynucleoside kinase and a nucleotidase, participating in the regulationof dNTP pools. Adenosine deaminase and phosphorylase, which could degradedeoxyribonucleoside, attain special importance in cells of the lymphoidsystem that are low in deoxyribonucleotidase activity, and, in their absence,dATP and dGTP specifically accumulate in B and T cells and cause diseases.Interaction between HCV NS3 and dNT-1 proteins was futhur demonstratedby IP-Western and confocal microscope analysis. We also discovered that dNT-1has no effect on the HCV replication and protein processing. On the otherhand, when HCV subgenomic replicon treated with IFN, the expression of dNT-1was altered, but the activity of dNT-1 was accelerated. The dNT-1 activitywas not affected by interferon treatment in Huh7 cell. These observationsreveal that HCV would inhibit dNT-1 activity possibly through NS3 protein.Our results suggest that the development of B cell lymphoma after HCVinfection possible through inhibition of dNT-1 activity.
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