Li Hong, Cunha Cristina W, Davies Christopher J, Gailbreath Katherine L, Knowles Donald P, Oaks J Lindsay, Taus Naomi S
Animal Diseases Research Unit, United States Department of Agriculture-Agriculture Research Service, Washington Sate University, Pullman, WA 99164, USA.
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA.
J Gen Virol. 2008 Jul;89(Pt 7):1699-1708. doi: 10.1099/vir.0.2008/000554-0.
Ovine herpesvirus 2 (OvHV-2), a rhadinovirus in the subfamily Gammaherpesvirinae, is the causative agent of sheep-associated malignant catarrhal fever (SA-MCF), a frequently fatal lymphoproliferative disease primarily of ruminants worldwide. Inability to propagate the virus in vitro has made it difficult to study OvHV-2 replication. Aerosol inoculation of sheep with OvHV-2 from nasal secretions collected from naturally infected sheep during shedding episodes results in infection of naive sheep, providing an excellent system to study OvHV-2 initial replication in the natural host. In this study, we showed that OvHV-2 delivered through the nasal route by nebulization resulted in infection in all lambs, but no infection was established in any lambs after intravenous or intraperitoneal injection. In nebulized lambs, while it was not detected initially in any other tissues, OvHV-2 DNA became detectable in the lung at 3 days post-infection (p.i.), increased to about 900 copies per 50 ng DNA at 5 days p.i., reached peak levels ( approximately 7500 copies) at 7 days p.i., and then declined to an average of 800 copies at 9 days p.i. Transcripts of OvHV-2 open reading frame 25 (coding for the capsid protein), an indicator of virus replication, were only detected in lung tissues, and were positively correlated with OvHV-2 DNA levels in the lungs. In addition, selected immune response genes were also highly expressed in the lung at 5 and 7 days p.i. The data indicate that lung is the primary replication site for OvHV-2 during initial infection in sheep and suggest that viral replication is promptly controlled by a host defence mechanism.
绵羊疱疹病毒2型（OvHV-2）是γ-疱疹病毒亚科的一种嗜淋巴细胞病毒，是绵羊相关恶性卡他热（SA-MCF）的病原体，SA-MCF是一种主要发生在全球反刍动物中的常见致命性淋巴细胞增生性疾病。由于无法在体外培养该病毒，使得对OvHV-2复制的研究变得困难。在病毒排出期，用从自然感染绵羊收集的鼻分泌物中的OvHV-2气溶胶接种绵羊，可使未感染的绵羊感染，这为研究OvHV-2在天然宿主中的初始复制提供了一个极佳的系统。在本研究中，我们发现通过雾化经鼻途径递送的OvHV-2可使所有羔羊感染，但静脉注射或腹腔注射后，无一羔羊感染。在雾化接种的羔羊中，虽然最初在任何其他组织中均未检测到OvHV-2 DNA，但在感染后3天（p.i.）可在肺中检测到，在感染后5天，每50 ng DNA中增加到约900拷贝，在感染后7天达到峰值水平（约7500拷贝），然后在感染后9天降至平均800拷贝。OvHV-2开放阅读框25（编码衣壳蛋白）的转录本是病毒复制的一个指标，仅在肺组织中检测到，并且与肺中OvHV-2 DNA水平呈正相关。此外，在感染后5天和7天，选定的免疫反应基因在肺中也高度表达。这些数据表明，肺是绵羊初次感染期间OvHV-2的主要复制部位，并表明病毒复制迅速受到宿主防御机制的控制。
