Analysis of a novel strain of murine gammaherpesvirus reveals a genomic locus important for acute pathogenesis
Analysis of a novel strain of murine gammaherpesvirus reveals a genomic locus important for acute pathogenesis
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DOI：
10.1128/jvi.75.11.5315-5327.2001
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发表时间：
2001-06-01
影响因子：
5.4
通讯作者：
Stewart, JP
中科院分区：
文献类型：
--
作者：
Macrae, AI;Dutia, BM;Stewart, JP
小鼠γ疱疹病毒68 （MHV-68）感染小鼠是研究γ疱疹病毒在自然宿主中发病机制的良好小动物模型。我们对另一种疱疹病毒，鼠疱疹病毒76 （MHV-76）进行了比较研究，该病毒与MHV-68同时分离，但来自不同的宿主黄颈鼠（Apodemus flavicollis）。分子分析表明，MHV-76基因组基本上与MHV-68相同，除了在独特区域的左端缺失了9538 bp。因此MHV-76是一个缺失突变体，缺少MHV-68特有的4个基因（M1、M2、M3和M4）以及8个病毒trna样基因。MHV-76在细胞培养中的复制与MHV-68相同，然而，在小鼠感染后，MHV-76从肺部被更快地清除。与此相一致的是，MHV-76感染后肺部的炎症反应增加，脾脏肿大也明显减少，脾脏中检测到的潜伏MHV-76要少得多。然而，MHV-76在肺和脾脏中保持长期潜伏期。我们利用含有MHV-68基因组左端的cosmid将缺失的序列通过重组插入到感染细胞的MHV-76中，并分离出一种表面上与MHV-68基因相同的援救病毒MHV-76(cA8+)4，该援救病毒在感染小鼠体内的生长特性与MHV-68完全相同。MHV-68基因组独特区域的左端在宿主逃避中起着至关重要的作用，并且对脾病理的发展至关重要。
Infection of mice by murine gammaherpesvirus 68 (MHV-68) is an excellent small-animal model of gammaherpesvirus pathogenesis in a natural host. We have carried out comparative studies of another herpesvirus, murine herpesvirus 76 (MHV-76), which was isolated at the same time as MHV-68 but from a different murid host, the yellow-necked mouse (Apodemus flavicollis), Molecular analyses revealed that the MHV-76 genome is essentially identical to that of MHV-68, except for deletion of 9,538 bp at the left end of the unique region. MHV-76 is therefore a deletion mutant that lacks four genes unique to MHV-68 (M1, M2, M3, and M4) as well as the eight: viral tRNA-like genes. Replication of MHV-76 in cell culture was identical to that of MHV-68, However, following infection of mice, MHV-76 was cleared more rapidly from the lungs. In line with this, there was an increased inflammatory response in lungs with MHV-76, Splenomegaly was also significantly reduced following MHV-76 infection, and much less latent MHV-76 was detected in the spleen. Nevertheless, MHV-76 maintained long-term latency in the lungs and spleen. We utilized a cosmid containing the left end of the MHV-68 genome to reinsert the deleted sequence into MHV-76 by recombination in infected cells, and we isolated a rescuant virus designated MHV-76(cA8+)4 which was ostensibly genetically identical to MHV-68, The growth properties of the rescuant in infected mice were identical to those of MHV-68, These results demonstrate that genetic elements at: the left end of the unique region of the MHV-68 genome play vital roles in host evasion and are critical to the development of splenic pathology.