Patel Swapneel J, Zhao Guoyan, Penna Vinay R, Park Eugene, Lauron Elvin J, Harvey Ian B, Beatty Wandy L, Plougastel-Douglas Beatrice, Poursine-Laurent Jennifer, Fremont Daved H, Wang David, Yokoyama Wayne M
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
J Virol. 2017 Apr 13;91(9). doi: 10.1128/JVI.02463-16. Print 2017 May 1.
The human roseoloviruses human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 comprise the genus of the human subfamily. Infections with these viruses have been implicated in many diseases; however, it has been challenging to establish infections with roseoloviruses as direct drivers of pathology, because they are nearly ubiquitous and display species-specific tropism. Furthermore, controlled study of infection has been hampered by the lack of experimental models, and until now, a mouse roseolovirus has not been identified. Herein we describe a virus that causes severe thymic necrosis in neonatal mice, characterized by a loss of CD4 T cells. These phenotypes resemble those caused by the previously described mouse thymic virus (MTV), a putative herpesvirus that has not been molecularly characterized. By next-generation sequencing of infected tissue homogenates, we assembled a contiguous 174-kb genome sequence containing 128 unique predicted open reading frames (ORFs), many of which were most closely related to herpesvirus genes. Moreover, the structure of the virus genome and phylogenetic analysis of multiple genes strongly suggested that this virus is a betaherpesvirus more closely related to the roseoloviruses, HHV-6A, HHV-6B, and HHV-7, than to another murine betaherpesvirus, mouse cytomegalovirus (MCMV). As such, we have named this virus murine roseolovirus (MRV) because these data strongly suggest that MRV is a mouse homolog of HHV-6A, HHV-6B, and HHV-7. Herein we describe the complete genome sequence of a novel murine herpesvirus. By sequence and phylogenetic analyses, we show that it is a betaherpesvirus most closely related to the roseoloviruses, human herpesviruses 6A, 6B, and 7. These data combined with physiological similarities with human roseoloviruses collectively suggest that this virus is a murine roseolovirus (MRV), the first definitively described rodent roseolovirus, to our knowledge. Many biological and clinical ramifications of roseolovirus infection in humans have been hypothesized, but studies showing definitive causative relationships between infection and disease susceptibility are lacking. Here we show that MRV infects the thymus and causes T-cell depletion, suggesting that other roseoloviruses may have similar properties.
人玫瑰疹病毒，即人类疱疹病毒6A（HHV - 6A）、HHV - 6B和HHV - 7，属于人类疱疹病毒亚科。这些病毒的感染与多种疾病有关；然而，要确定玫瑰疹病毒感染是疾病发生的直接驱动因素具有挑战性，因为它们几乎无处不在且表现出种属特异性嗜性。此外，由于缺乏实验模型，对感染的对照研究受到阻碍，并且直到现在，尚未鉴定出小鼠玫瑰疹病毒。在此，我们描述了一种可导致新生小鼠严重胸腺坏死的病毒，其特征是CD4 T细胞缺失。这些表型与先前描述的小鼠胸腺病毒（MTV）引起的表型相似，MTV是一种尚未进行分子特征鉴定的假定疱疹病毒。通过对感染组织匀浆进行二代测序，我们组装出了一个连续的174 kb基因组序列，其中包含128个独特的预测开放阅读框（ORF），其中许多与疱疹病毒基因关系最为密切。此外，病毒基因组的结构以及多个基因的系统发育分析强烈表明，该病毒是一种β疱疹病毒，与玫瑰疹病毒、HHV - 6A、HHV - 6B和HHV - 7的亲缘关系比与另一种鼠β疱疹病毒——小鼠巨细胞病毒（MCMV）更为密切。因此，我们将这种病毒命名为小鼠玫瑰疹病毒（MRV），因为这些数据强烈表明MRV是HHV - 6A、HHV - 6B和HHV - 7的小鼠同源物。在此，我们描述了一种新型鼠疱疹病毒的完整基因组序列。通过序列和系统发育分析，我们表明它是一种β疱疹病毒，与玫瑰疹病毒、人类疱疹病毒6A、6B和7关系最为密切。这些数据与人类玫瑰疹病毒在生理上的相似性共同表明，这种病毒是小鼠玫瑰疹病毒（MRV），据我们所知，它是首个得到明确描述的啮齿动物玫瑰疹病毒。人们已经对玫瑰疹病毒感染在人类中的许多生物学和临床影响进行了推测，但缺乏显示感染与疾病易感性之间明确因果关系的确切研究。在此我们表明，MRV感染胸腺并导致T细胞耗竭，这表明其他玫瑰疹病毒可能具有类似特性。
