MOLECULAR PATHOGENESIS OF VARICELLA ZOSTER VIRUS INFECTION

水痘带状疱疹病毒感染的分子发病机制

• 批准号: 8172923
• 负责人: VICKI L TRAINA-DORGE
• 金额: $ 6.18万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172923
• 关键词: Animals; Autopsy; Blood Circulation; Cercopithecus pygerythrus; Chickenpox; Clinical; Computer Retrieval of Information on Scientific Projects Database; Exanthema; Funding; Ganglia; Grant; Herpesvirus Type 3; Human; Immunosuppression; Infection; Institution; Liver; Lung; Macaca mulatta; Modeling; Molecular; Monkeys; Myxoid cyst; Nerve Tissue; Pathogenesis; Peripheral; Research; Research Personnel; Resources; Source; Spinal Ganglia; Testing; United States National Institutes of Health; Virus; Virus Diseases; Work; irradiation; nonhuman primate; reactivation from latency; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Monkeys can be infected with simian varicella virus (SVV), with clinical, pathological, immunological and virological features virtually identical to those of VZV infection in humans. Also similar to humans, following 8-12 weeks post infection, the virus becomes latent in the dorsal root ganglia and have the potential to reactivate. Our earlier work developed a latency/reactivation model in the African green monkey. Latently-infected AGM were tested by immunosuppression and X-irradiation and were shown to initiate SVV reactivation. The nonhuman primate model was originally developed in the AGM as a natural transmission model. SVV-seronegative monkeys were exposed as cagemates to other monkeys that had been inoculated with SVV. The inoculated monkeys became infected, developed chickenpox but virus persisted for weeks/months in the peripheral circulation, lungs, and liver. The exposed monkeys, however, developed chickenpox but were able to clear virus from the bloodstream quickly and by 8-12 weeks, virus was found only in nerve tissue but not in lung or liver. A typical study consisted of 8 animals: 3 inoculated and 5 exposed. A recent study by Messaoudi et al., 2009, proposed that SVV infection in rhesus macaque results in a similar latency rather than persistent infection. Due to the needed use of increased numbers of animals to accomplish natural exposure, we wanted to confirm these findings. A small study was conducted in rhesus macaque to test the ability of another species to develop latency following direct inoculation of SVV. Two seronegative rhesus macaques were intratracheal inoculated with 1 x 10e4 SVV and followed for virolgical and clinical findings. Both animals were infected, developed typical chickenpox rash, and circulating virus peaking at d12 post inoculation. We followed the animals for 14 weeks and demonstrated significant clearance of virus by 8 weeks suggesting latency. We conducted necropsy of both animals and are currently assessing levels of virus in lung, liver and ganglia for final confirmation of latency. If they are finally confirmed, we will switch to the rhesus for use in conducting the remaining studies proposed in this grant.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 猴子可以感染猿猴水痘病毒（SVV），其临床，病理，免疫学和病毒学特征几乎与人类的VZV感染几乎相同。同样与人类相似，感染后8-12周后，该病毒在背根神经节中变得潜在，并具有重新激活的潜力。我们较早的工作在非洲绿猴中开发了一种潜伏/重新激活模型。通过免疫抑制和X-辐射测试了潜在感染的AGM，并显示出启动SVV重新激活。非人类灵长类动物模型最初是在AGM中作为自然传输模型开发的。 将SVV副猴子暴露于接种SVV的其他猴子。接种的猴子被感染，开发了水痘，但病毒在周围循环，肺部和肝脏中持续数周/几个月。然而，暴露的猴子出现了水痘，但能够快速清除血液中的病毒，到8-12周，仅在神经组织中发现病毒，但在肺或肝脏中没有发现病毒。一项典型的研究由8只动物组成：3种接种和5个暴露。 Messaoudi等人2009年最近的一项研究提出，恒河猴中的SVV感染会导致相似的潜伏期而不是持续的感染。 由于需要增加动物数量来实现自然暴露，因此我们想确认这些发现。在恒河猴中进行了一项小型研究，以测试直接接种SVV后另一种物种发展潜伏期的能力。气体内接种了1 x 10E4 SVV的气管内两个血清念珠猕猴，然后进行病毒和临床发现。 两种动物都被感染，发展为典型的水痘皮疹，并在接种后D12时循环病毒峰值。我们跟随动物14周，并在8周之前证明了病毒的显着清除，表明潜伏期。我们对两种动物进行了尸检，目前正在评估肺，肝脏和神经节病毒水平，以最终确认潜伏期。如果最终确认它们，我们将改用恒河猴，用于进行本赠款中提出的其余研究。