Virus Receptors and Cytokines

病毒受体和细胞因子

• 批准号: 10044279
• 负责人: TASHIRO Kei
• 金额: $ 3.07万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10044279/
• 关键词: AIDS; SDF-1; Cytokine; CXCR4; HIV-1; Polymorphysm; receotor; TR-FLA; ポリモルフィズム

Collaboration was done with Dr.Verma (SALK Institute, U.S.A.), Dr.O'Brien (NCI, U.S.A.), Dr. Durandy (INSERM, France) and their colleagues on a cytokine, SDF-1, which is the natural ligand for CXCR4, the coreceptor for T tropic HIV virus.1. To understand molecular mechanism of our finding that AIDS onset is delayed in the persons who bear homozygous alleles of SDF1 gene AIDS delaying type polymorphysm, the blood SDF-1 concentration in each individuals bearing each genotype was measured. For that, new measuring system named SDF-1 TR-FIA was developed in collaboration with Dr.Matsumoto (Waseda Univ./CREST) and blood samples were collected by Dr.O'Brien. The measuring work is still on going.2. In our SDF-1 expression system in vivo, CXCR4 on CD4ィイD1+ィエD1 cells were down-modulated in the presence of excess amount of SDF-1, showing the molecular mechanism of the delay.3. We are screening additional polymorphic site linked with the SDF1 gene AIDS delaying type polymorphysm.

与Verma博士（SALK研究所，美国）进行了合作，奥布莱恩博士（美国国家癌症研究所），Durandy博士（法国CIMM）及其同事研究细胞因子SDF-1，SDF-1是嗜T HIV病毒的辅助受体CXCR 4的天然配体。为了解携带SDF-1基因纯合等位基因的艾滋病延迟型多形性体质患者发病延迟的分子机制，测定了携带各基因型患者的血SDF-1浓度。为此，与松本博士（早稻田大学/ CREST）和血液样本由奥布莱恩博士收集。测量工作仍在进行中.在我们的SDF-1体内表达系统中，CD 4 + CD 4 + CD 4 + D1细胞上的CXCR 4在过量的SDF-1存在下下调，显示了延迟的分子机制.我们正在筛选与SDF 1基因连锁的其他多态性位点。

项目成果

Moriya, C., et. al.: "Large quantity production with extreme convenience of human SDF-1α and SDF-1β by a Sendai virus vector"FEBS Lett.. 425. 105-111 (1998)

Moriya, C., et. al.：“通过仙台病毒载体极其方便地大量生产人类 SDF-1α 和 SDF-1β” FEBS Lett.. 425. 105-111 (1998)

Revy, P., et. al.: "A Syndrome Involving Intrauterine Growth Retardation, Microcephaly, Cerebellar Hypoplasia, B Lymphocyte Deficiency, and Progressive Pancytopenia"Pediatrics. 105. 22476-22483 (2000)

Revy，P.，等。

Revy,P., et al.: "A Syndrome Involving Intrauterine Growth Retardation, Microcephaly, Cerebellar Hypoplasia. B Lymphocyte Deficiency, and Progressive Pancytopenia"Pediatrics. 105. 22476-22483 (2000)

Revy，P.，等人：“涉及子宫内生长迟缓、小头畸形、小脑发育不全的综合征。B 淋巴细胞缺乏和进行性全血细胞减少症”儿科。

Winkler C.et.al.: "Genetic Restriction of AIDS Pathogenesis by an SDF-1 Chemokine Gene Variant"Science. 279. 389-393 (1998)

Winkler C.et.al.：“SDF-1 趋化因子基因变体对艾滋病发病机制的遗传限制”科学。

Shinoda,T., et al.: "Anti-HIV-1 and chemotactic activities of human stromal cell-derived factor 1α(SDF-1α) and SDF-1β are abolished by CD26/dipeptidyl peptidase IV-mediated cleavage"Proc. Natl. Acad. Sci. U.S.A.. 95. 6331-6336 (1998)

Shinoda, T. 等人：“CD26/二肽基肽酶 IV 介导的裂解消除了人基质细胞衍生因子 1α (SDF-1α) 和 SDF-1β 的抗 HIV-1 和趋化活性”Proc。美国科学。95。6331-6336（1998）