| Co-Investigator(Kenkyū-buntansha) |
HASEGAWA Atsuhiko Nihon University, Faculty of Bioresource Sciences, Professor, 生物資源科学部, 教授 (90011923)
MIYAZAWA Takayuki The University of Tokyo, Graduate School of Agricultural and Life Sciences, Assi, 大学院・農学生命科学研究科, 助手 (80282705)
WATARI Toshihiro The University of Tokyo, Graduate School of Agricultural and Life Sciences, Assi, 大学院・農学生命科学研究科, 助手 (50220950)
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| Research Abstract |
Nucleotide sequence analysis of feline imunodeficiency virus (FIV) env gene obtained from multiple districts in Japan showed that subtypes B and D viruses were predominant in the eastern and western parts of Japan, respectively, and subtypes A and C viruses were occasionally found in some specific areas. Molecular clones of feline CC-and CXC-chemokines, which have been identified as ligands of co-receptors for HIV, were isolated and characterized. Of these chemokines, SDF-1beta was shown to inhibit the growth of FIV in cat T-lymphoid cells. Moreover, T22, a newly synthesized compound which binds to CXC-chemokine receptor, also inhibited FIV growth.
On the other hand, apoptosis induced by FIV infection is known to play an important role for the pathogenesis of immunodeficiency. Antioxidants, N-acetylcysteine and ascorbic acid, were shown to inhibit apoptosis induced by FlV infection in vitro. Furthermore, IL-12 and IL-10 were added to the in vitro apoptosis-induction system by Fly. IL-12 was shown to inhibit FIV growth and apoptosis, however, IL-lO did not have such effect. The inhibitory effect of IL-12 for virus growth and apoptosis was found to be mediated by the expression of IFN-gamma.
Next, to examine the effect of these compounds for inhibition of FIV growth and apoptosis, plasma viral RNA load in FLY-infected cats was quantified with QC-PCR.As a result, the plasma viral RNA load was less than 105 copies/ml in cats in asymptomatic carrier stage but higher than 107 copies/ml in cats in AIDS stage. By using the quantification system for plasma FIV RNA, we are continueing the investigation on the kinetics of the viral RNA load and effect of anti-viral drugs in FIV-infected cats.
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