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显示，日本东部和西部地区分别以B和D亚型病毒为主，在一些特定地区偶见A和C亚型病毒。地区。猫科动物 CC 和 CXC 趋化因子的分子克隆已被鉴定为 HIV 共受体的配体，并进行了分离和表征。在这些趋化因子中，SDF-1β 可抑制猫 T 淋巴细胞中 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也能抑制FIV生长。另一方面，已知FIV感染诱导的细胞凋亡在免疫缺陷的发病机制中发挥重要作用。抗氧化剂 N-乙酰半胱氨酸和抗坏血酸在体外可抑制 FIV 感染诱导的细胞凋亡。此外，Fly将IL-12和IL-10添加到体外凋亡诱导系统中。 IL-12显示抑制FIV生长和细胞凋亡，然而，IL-10没有这样的作用。 IL-12对病毒生长和凋亡的抑制作用被发现是通过IFN-γ的表达介导的。接下来，为了检查这些化合物对FIV生长和凋亡的抑制作用，FLY感染的血浆病毒RNA载量采用QC-PCR对猫进行定量。结果，无症状携带者阶段的猫血浆病毒RNA载量低于105拷贝/ml，但艾滋病阶段的猫血浆病毒RNA载量高于107拷贝/ml。通过使用血浆 FIV RNA 定量系统，我们正在继续研究 FIV 感染猫中病毒 RNA 载量的动力学和抗病毒药物的效果。

项目成果

Endo,Y., et al.: "Molecular characteristics of malignant lymphomas in cats naturally infected with feline immunodeficiency virus." Veterinary Immunology and Immunopathology. 57. 153-167 (1997)

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。”

Mizuno, T.et al.: "Molecular cloning of feline Fas antigen and Fas ligand cDNAs." Vet.Immunol.Immunopathol. 65. 161-172 (1998)

Mizuno, T.等人：“猫科动物 Fas 抗原和 Fas 配体 cDNA 的分子克隆。”

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.et al：“6 例猫颗粒淋巴细胞瘤的临床病理学和免疫学特征。”

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）。