A study on the prevention and treanment of feline immunodeficiency virus infection

猫免疫缺陷病毒感染的防治研究

• 批准号: 09460144
• 负责人: TSUJIMOTO Hajime
• 金额: $ 8.58万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09460144/
• 关键词: Feline immunodeficiency virus; Subtype; Chemokine; SDF-1B; Apoptosis; IL-12; Viral load; QC-PCR; ネコ免疫不全ウイルス; ワクチン; ウイルス増殖抑制剤; サイトカイン; エンベロープ蛋白; 抗酸化剤

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.

对从日本多个地区获得的猫免疫缺陷病毒(FIV)env基因的核苷酸序列分析表明，日本东部和西部地区分别以B和D亚型病毒为主，个别地区偶尔发现A和C亚型病毒。分离并鉴定了猫CC-和CXC-趋化因子的分子克隆，它们是HIV辅助受体的配基。在这些趋化因子中，SDF-1β可抑制猫T淋巴样细胞中FIV的生长。此外，新合成的与CXC-趋化因子受体结合的化合物T22也抑制了FIV的生长，另一方面，FIV感染诱导的细胞凋亡在免疫缺陷的发病机制中发挥了重要作用。体外实验表明，抗氧化剂N-乙酰半胱氨酸和抗坏血酸可抑制流感病毒感染诱导的细胞凋亡。此外，将IL-12和IL-10加入苍蝇体外诱导细胞凋亡系统中。IL-12可抑制FIV增殖和细胞凋亡，而IL-LO则无此作用。IL-12对病毒增殖和细胞凋亡的抑制作用是通过干扰素-γ的表达来实现的。接下来，为了检测这些化合物对FIV生长和细胞凋亡的抑制作用，用QC-PCR法测定了感染苍蝇的猫的血浆病毒RNA载量，结果表明，无症状携带期的猫血浆病毒RNA载量小于105拷贝/毫升，而艾滋病猫的血浆病毒RNA载量高于107拷贝/毫升。利用血浆FIV RNA定量系统，我们正在继续研究FIV感染猫体内病毒RNA载量的动态变化和抗病毒药物的作用。

项目成果

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Endo,Y. 等人：“自然感染猫免疫缺陷病毒的猫恶性淋巴瘤的分子特征。”

Endo, Y.et al.: "Clinocopathological and immunological characteristics of 6 cases with granular lymphocyte tumors in cats." Comp.Immunol.Microbiol Infec.Dis.21. 27-42 (1998)

Endo, Y. 等人：“6 例猫颗粒淋巴细胞瘤的临床病理学和免疫学特征。”

Cho,K.W., et al.: "Assignment of feline immunoglobulin heavy chain gene to chronosome B3q26 and T'cell receptor gamma chain gene to A2q12-q13." Cytogenetics and Cell Genetics. (印刷中). (1998)

Cho, K.W., 等人：“猫免疫球蛋白重链基因分配给染色体 B3q26，T 细胞受体伽玛链基因分配给 A2q12-q13。”（细胞遗传学和细胞遗传学）。

Mortola,E.et al: "Inhibition of apoptosis and virus replication in feline immunodeficiency virus-infected cells by N-acetylcysteine and ascorbic acid." J.Vet.Med.Sci.60. 1187-1193 (1998)

Mortola,E.等人：“N-乙酰半胱氨酸和抗坏血酸抑制猫免疫缺陷病毒感染细胞的细胞凋亡和病毒复制。”

Mizuno,T., et al.: "Molecular cloning of feline Fas autigen and Fas ligand and their expression in feline immunodeficiency virus infection." Veterinary Immunology and Immunopathology. (印刷中). (1998)

Mizuno, T., et al.：“猫科动物 Fas autigen 和 Fas 配体的分子克隆及其在猫科动物免疫缺陷病毒感染中的表达。”（兽医免疫学和免疫病理学）（1998 年出版）。