HHV 8 INFECTION IN RHESUS MACAQUES

意义HHV-8感染的非人类灵长类动物模型将是 对阐明病毒致病机制和病毒的致病机制具有重要意义 抗病毒药物和疫苗的开发。这方面的初步研究 项目表明可以获得低水平的持续感染 接种HHV-8病毒颗粒的恒河猴。目标人类 8型疱疹病毒(HHV-8)，又称卡波西氏肉瘤疱疹 病毒(KSHV)是一种新发现的人类病毒，已经 与卡波西氏肉瘤和其他肿瘤(如体腔)有关 在感染艾滋病毒的艾滋病患者中发生了严重的癌症(淋巴瘤)。一种可以研究的动物模型 病毒致病机制及检测抗病毒药物和 目前还没有针对HHV-8的疫苗。因此，开展了一项试点研究 以确定恒河猴是否会感染 HHV-8。结果该病毒疫苗由从日本血吸虫中分离的病毒组成。 人B细胞系的培养液，可诱导 产生HHV-8颗粒。两只健康的幼年猕猴 通过静脉途径接种这种接种剂。分析 聚合酶链式反应(PCR)检测外周血淋巴细胞 病毒特异性引物，揭示了病毒DNA存在了超过 感染一年后。这两只动物都保持健康，没有 肿瘤的迹象。另外两只幼年猕猴，长期 感染致病SIVmac251的儿童接种HHV-8 静脉注射，接种量与上述相同。每一个SIV 携带HHV-8DNA的携带者通过对 外周血淋巴细胞。在一年内，这两只动物 患上了一种致命的类似艾滋病的疾病。尸检分析没有显示 内皮细胞异常或肿瘤。未来方向二 实验计划继续努力开发一种非人类 HHV-8感染的灵长类动物模型和(潜在)发病机制。 首先，新生恒河猴将接种HHV-8；新生儿 动物通常在免疫方面还不成熟，而且可能比 易感染的易受感染的第二，成年长尾猴，一只 新世界物种，将接种HHV-8；这一想法 初步研究的基础是观察到某些疱疹病毒 来自东半球的灵长类动物会在东半球灵长类动物中引起疾病。钥匙 HHV-8，疫苗基金加州大学可自由支配基金

Significance A non-human primate model for HHV-8 infection will be significant for elucidating mechanisms of viral pathogenesis and the development of antiviral drugs and vaccines. Pilot studies in this project indicate that a low-level persistent infection can be obtained in rhesus macaques inoculated with HHV-8 particles. Objectives Human herpes virus type-8 (HHV-8), also known as Kaposi's sarcoma herpes virus (KSHV) is a newly identified human virus that has been implicated in Kaposi's sarcoma and other neoplasms (e.g., body cavity lymphoma) in HIV-infected AIDS patients. An animal model to study mechanisms of viral pathogenesis and to test anti-viral drugs and vaccines is not available for HHV-8. Accordingly, a pilot study was performed to determine whether rhesus macaques could be infected with HHV-8. Results The virus inoculum consisted of virus obtained from the culture medium of a human B-cell line which can be induced to produce HHV-8 particles. Two healthy juvenile macaques were inoculated by the intravenous route with this inoculum. Analysis of peripheral blood lymphocytes by polymerase chain reaction (PCR), with viral-specific primers, revealed that viral DNA was present for over one year after infection. Both animals have remained healthy with no signs of neoplasia. Two additional juvenile macaques, chronically infected with pathogenic SIVmac251, were inoculated with HHV-8 by the intravenous route with the same inoculum as above. Each of these SIV carriers contained HHV-8 DNA as demonstrated by PCR analysis of peripheral blood lymphocytes. Within one year, both of these animals developed a fatal AIDS-like disease. Necropsy analysis did not reveal endothelial cell abnormalities or neoplasia. Future Directions Two experiments are planned to continue efforts at developing a non-human primate model for HHV-8 infection and (potential) pathogenesis. First, newborn rhesus macaques will be inoculated with HHV-8; newborn animals are generally immunologically immature and may be more susceptible to infection. Second, adult Callicebus (titi) monkeys, a New World species, will be inoculated with HHV-8; the idea for this pilot study is based on the observation that certain herpes viruses from Old World primates cause disease in New World primates. KEY WORDS HHV-8, vaccine FUNDING UC Discretionary Funds