| Co-Investigator(Kenkyū-buntansha) |
IWAKURA Yoichiro University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (10089120)
BABA Masanori Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (70181039)
MITSUYA Hiroaki Kumamoto University, Faculty of Medicine, Professor, 医学部, 教授 (20136724)
TANAKA Yuetsu University of the Ryukyus, Faculty of Medicine, Professor, 医学部, 教授 (30163588)
FUJII Nobutaka Kyoto University, Graduate School of Medicine, Professor, 薬学研究科, 教授 (60109014)
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| Research Abstract |
Mitsuya had developed a novel CCR5 inhibitor, E913, and shown that the combination of this drug with AMD3100 suppressed the replication of dual tropic virus synergistically. Mitsuya also analyzed the structural biology of LD78β and reported that the replacement of certain amino acid facilitated the anti-viral activity of this chemokine. Baba isolated a virus clone resistant to CCR5 antagonist, TAK-779, analyzed mutations in the gp120 gene of this clone, and found that mutations in V3 region facilitated the affinity of gp120 to CCR5, resulting in the resistance to TAK-779. Fujii developed a potent and selective inhibitor for CXCR4, T140, and a membrane fusion inhibitor, SC34, and analyzed the drug resistance using SC34 as a molecular probe. Iwakura established a Vpr transgenic mouse and showed that peripheral T cells decreased in number by 1/20 in this mouse, suggesting that Vpr might be involved in the depletion of peripheral T cells. Tanaka reported that immunized SCID-PBL mice with dendritic cells from the same donor pulsed with inactivated HIV-1 showed the resistance to R5 HIV-1 challenge, Matsushita analyzed the activity of neutralizing antibodies in infected patients, and found that 4 cases among 19 patients showed the upregulation of neutralizing activities more than 1 year after introduction of HAART. He also reported that virus escape from neutralizing antibody in vivo was associated with the mutations in the C3 region as well as the variable regions of gp120.
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