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Studies on the mechanisms of persistent infection and reactivation of animal viruses.

动物病毒持续感染和再激活机制研究。

基本信息

批准号：
06404015
负责人：
MIKAMI Takeshi
金额：
$ 17.92万
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 (A)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1999
项目状态：
已结题

项目摘要

In persistent infection, virus can hidden in body and escape from immunological pressure, in spite of the presence of immunity. However, the virus is sometimes reactivated to produce diseases in host. Following results were obtained.1.We established an in vitro model for a persistent infection of feline immunodeficiency virus (FIV) using a human T-lymphoid cell line (MOLT-4). FIV-specific RNA expression could not be detected in the infected MOLT-4 cells, suggesting that the viral replication was blocked in the early stage of virus life-cycle. Furthemore, it was demonstrated that infectious virus was rescued by treatment of the infected MOLT-4 cells with a phorbol ester (TPA).2.Three specific pathogen-free cats experimentally infected with FIV subtypes A (Petaluma strain) and B (TM1 and TM2 strains) respectively were observed for over 8 years. The cat infected with FIV subtype A died with hemoperitoneum at 8 years and 8 months post-infection (p.i.), while those with FIV subtype B are st … More ill clinically healthy over 9 years p.i.. In persistent infection of FIV,the difference of pathogenicity among subtypes and the environment where animals kept were suggested to be important factors to develop AIDS.3.Marek's disease virus (MDV) can be serologically and genetically devided into 3 serotypes and all cause persistent infection in chickens. MDV-1 is oncogenic whereas MDV-2 is non-oncogenic. To understand the mechanisms of persistent infection and oncogenicity at genetic levels, we sequenced over 90% of MDV-2 genome.4.The immediate-early (IE) gene products of herpesviruses are thought to play an important role in regulating latent infection. We demonstrated that feline herpesvirus type 1 (FHV-1) produced a single immediate-early (IE) transcript encoding FHV-1 ICP4 and that FHV-1 ICP4 gene was alternatively regulated by the two promoters. Furthermore, it was shown that a negative regulatory element, which was composed of a 20 bp direct repeat unit, was located between the two promoters.5.A persistently infected B95a cell line with the Yanaka strain of CDV was established. The virus recovered from this carrier culture has infectivity to fresh B95a cells, and causes persistent infection without showing CPE.This virus was designated as the Yanaka-BP strain. Immunoprecipitation revealed identical molecular mass of the H or F proteins of the Yanaka and Yanaka-BP strains. Sequence analysis of the F gene showed that the third in-frame ATG triplet which considered to be selectively required for in vitro translation of the Onderstepoort F gene was lacked in the Yanaka-BP strain. Less

在持续感染时，尽管存在免疫力，病毒仍可以隐藏在体内并逃避免疫压力。然而，病毒有时会重新激活，在宿主体内产生疾病。获得以下结果：1.利用人T淋巴细胞系(MOLT-4)建立了猫免疫缺陷病毒(FIV)持续感染的体外模型。在受感染的MOLT-4细胞中未检测到FIV特异性RNA表达，表明病毒复制在病毒生命周期的早期被阻断。此外，还证明，用佛波酯（TPA）处理感染的MOLT-4细胞可以挽救感染性病毒。2.对分别感染FIV亚型A（Petaluma株）和B（TM1和TM2株）的三只特定无病原体猫进行了8年多的观察。感染FIV A亚型的猫在感染后8年零8个月时因腹腔积血死亡，而感染FIV B亚型的猫则在感染后9年以上临床健康。在FIV持续感染中，亚型之间的致病性差异和动物饲养环境被认为是发展艾滋病的重要因素。 3.马立克氏病病毒（MDV）可从血清学和血清学角度观察。基因上分为 3 种血清型，所有血清型都会引起鸡的持续感染。 MDV-1 是致癌性的，而 MDV-2 是非致癌性的。为了在基因水平上了解持续感染和致癌性的机制，我们对90%以上的MDV-2基因组进行了测序。4.疱疹病毒的立即早期（IE）基因产物被认为在调节潜伏感染中发挥着重要作用。我们证明猫疱疹病毒 1 型 (FHV-1) 产生编码 FHV-1 ICP4 的单个立即早期 (IE) 转录本，并且 FHV-1 ICP4 基因交替受到两个启动子的调控。此外，还发现两个启动子之间存在一个由20 bp同向重复单元组成的负调控元件。5.建立了CDV Yanaka株持续感染的B95a细胞系。从该载体培养物中回收的病毒对新鲜的B95a细胞具有感染性，并且引起持续感染而不表现出CPE。该病毒被指定为Yanaka-BP株。免疫沉淀显示 Yanaka 和 Yanaka-BP 菌株的 H 或 F 蛋白分子质量相同。 F基因的序列分析显示，Yanaka-BP菌株中缺乏被认为是Onderstepoort F基因体外翻译选择性需要的第三个框内ATG三联体。较少的