Aligo Jason, Brosnan Kerry, Walker Mindi, Emmell Eva, Mikkelsen S Rochelle, Burleson Gary R, Burleson Florence G, Volk Amy, Weinstock Daniel
Biologics Toxicology, Janssen Research and Development, LLC , Spring House, PA , USA and.
J Immunotoxicol. 2015;12(4):330-41. doi: 10.3109/1547691X.2014.980020. Epub 2014 Nov 21.
Murine gammaherpesvirus-68 (MHV-68), a natural pathogen of mice, is being evaluated as a model of Epstein Barr Virus (EBV) infection for use in investigation of the effects of immunomodulatory therapy on herpesvirus pathogenesis in humans. Immunosuppressive agents are used for treatment of a variety of autoimmune diseases as well as for prevention of tissue rejection after organ transplantation and can result in recrudescence of latent herpesvirus infections. Prior to examination of MHV-68 as a suitable model for EBV, better characterization of the MHV-68 model was desirable. Characterization of the MHV-68 model involved development of assays for detecting virus and for demonstration of safety when present in murine colonies. Limited information is available in the literature regarding MHV-68 transmission, although recent reports indicate the virus is not horizontally spread in research facilities. To further determine transmission potential, immunocompetent and immunodeficient mice were infected with MHV-68 and co-habitated with naïve animals. Molecular pathology assays were developed to characterize the MHV-68 model and to determine viral transmission. Horizontal transmission of virus was not observed from infected animals to naïve cagemates after fluorescence microscopy assays and quantitative PCR (qPCR). Serologic analysis complemented these studies and was used as a method of monitoring infection amongst murine colonies. Overall, these findings demonstrate that MHV-68 infection can be controlled and monitored in murine research facilities, and the potential for unintentional infection is low.
鼠γ-疱疹病毒68型(MHV-68)是小鼠的一种天然病原体,正被评估作为爱泼斯坦-巴尔病毒(EBV)感染的模型,用于研究免疫调节疗法对人类疱疹病毒发病机制的影响。免疫抑制剂用于治疗多种自身免疫性疾病以及预防器官移植后的组织排斥反应,可导致潜伏性疱疹病毒感染复发。在将MHV-68作为EBV的合适模型进行研究之前,需要对MHV-68模型进行更好的表征。对MHV-68模型的表征包括开发检测病毒的方法以及证明其在鼠群中存在时的安全性。关于MHV-68传播的文献资料有限,尽管最近的报告表明该病毒在研究设施中不会水平传播。为了进一步确定传播潜力,将具有免疫能力和免疫缺陷的小鼠感染MHV-68,并与未感染的动物共同饲养。开发了分子病理学检测方法来表征MHV-68模型并确定病毒传播情况。在荧光显微镜检测和定量PCR(qPCR)后,未观察到病毒从感染动物水平传播至未感染的同笼动物。血清学分析补充了这些研究,并被用作监测鼠群中感染情况的一种方法。总体而言,这些发现表明,在鼠类研究设施中,MHV-68感染可以得到控制和监测,无意感染的可能性较低。