A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion.
A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion.
复制标题
一种与普遍存在的人类疱疹病毒密切相关的鼠疱疹病毒会导致 T 细胞耗竭。
DOI：
10.1128/jvi.02463-16
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发表时间：
2017
影响因子：
5.4
通讯作者：
Yokoyama,WayneM
中科院分区：
文献类型：
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作者：
Patel,SwapneelJ;Zhao,Guoyan;Penna,VinayR;Park,Eugene;Lauron,ElvinJ;Harvey,IanB;Beatty,WandyL;Plougastel-Douglas,Beatrice;Poursine-Laurent,Jennifer;Fremont,DavedH;Wang,David;Yokoyama,WayneM
人类玫瑰花状病毒人类疱疹病毒6A（HHV-6A）、HHV-6 B和HHV-7包含人类β疱疹病毒亚科的玫瑰花状病毒属。这些病毒的感染与许多疾病有关;然而，将玫瑰色病毒感染确定为病理学的直接驱动因素具有挑战性，因为它们几乎无处不在，并显示出物种特异性的嗜性。此外，由于缺乏实验模型，感染的对照研究受到阻碍，直到现在，还没有鉴定出小鼠玫瑰花状病毒。在此，我们描述了一种病毒，导致严重的胸腺坏死，在新生小鼠，其特点是损失的CD 4 +T细胞。这些表型类似于由先前描述的小鼠胸腺病毒（MTV）引起的表型，MTV是一种假定的疱疹病毒，尚未进行分子表征。通过对感染组织匀浆进行下一代测序，我们组装了一个连续的174 kb基因组序列，其中包含128个独特的预测开放阅读框架（ORF），其中许多与疱疹病毒基因最密切相关。此外，病毒基因组的结构和多个基因的系统发育分析强烈表明，这种病毒是一种β疱疹病毒更密切相关的玫瑰病毒，HHV-6A，HHV-6 B和HHV-7，比另一种鼠β疱疹病毒，小鼠巨细胞病毒（MCMV）。因此，我们将这种病毒命名为鼠玫瑰状病毒（MRV），因为这些数据强烈表明MRV是HHV-6A、HHV-6 B和HHV-7的小鼠同源物。重要说明在此，我们描述了一种新的鼠疱疹病毒的全基因组序列。通过序列分析和系统发育分析，我们发现它是一种β疱疹病毒，与玫瑰病毒，人类疱疹病毒6A，6 B和7最密切相关。这些数据结合与人玫瑰花状病毒的生理相似性共同表明，这种病毒是一种鼠玫瑰花状病毒（MRV），据我们所知，这是第一种明确描述的啮齿动物玫瑰花状病毒。许多生物学和临床分支玫瑰病毒感染人类已被假设，但研究表明感染和疾病易感性之间的明确因果关系是缺乏的。在这里，我们表明，MRV感染胸腺，并导致T细胞耗竭，这表明其他玫瑰病毒可能具有类似的特性。
The human roseoloviruses human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 comprise the Roseolovirus genus of the human Betaherpesvirinae 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.IMPORTANCEHerein 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.