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。目的人类疱疹 8型病毒(HHV-8)，又称卡波西肉瘤疱疹病毒 (KSHV)是一种新发现的人类病毒，它与 卡波氏肉瘤和其他肿瘤(如体腔淋巴瘤) 感染艾滋病毒的艾滋病患者。一种研究心力衰竭发病机制的动物模型 病毒的发病机制和测试抗病毒药物和疫苗是不可能的 适用于HHV-8病毒。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猪瘟病毒中分离到的病毒组成。 人B细胞系的培养基能被诱导产生 HHV-8颗粒。对两只健康的幼年猕猴进行了接种。 用这种疫苗进行静脉注射。外周血的分析 用病毒特异性的聚合酶链式反应(PCR)检测淋巴细胞 引子显示，病毒DNA在一年多后 感染。这两只动物都保持健康，没有任何迹象表明 肿瘤。另外两只幼年猕猴，慢性感染 用致病的SIVmac251疫苗接种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，一种 新世界物种，将接种HHV-8。关键词HHV-8， 疫苗

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. Objectives Human herpes virus type-8 (HHV-8), also known as Kaposis sarcoma herpes virus (KSHV) is a newly identified human virus that has been implicated in Kaposis 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 calicebus (titi) monkeys, a New World species, will be inoculated with HHV-8. KEYWORDS HHV-8, vaccine