Kinetic and phenotypic changes in murine lymphocytes infected with murine gammaherpesvirus-68 in vitro
Kinetic and phenotypic changes in murine lymphocytes infected with murine gammaherpesvirus-68 in vitro
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DOI：
10.1099/0022-1317-80-10-2729
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发表时间：
1999-10-01
影响因子：
3.8
通讯作者：
Hash, AA
中科院分区：
文献类型：
--
作者：
Dutia, BM;Stewart, JP;Hash, AA
与伽马疱疹病毒亚家族的其他成员一样，小鼠伽马疱疹病毒-68(MHV-68)的原发感染以淋巴增殖期为特征。MHV-68导致急性脾肿大和传染性单核细胞增多症，其中CD8(+)T细胞亚群扩张。在长期感染中，MHV-68与淋巴瘤的发展有关。为了阐明增殖过程的机制，我们研究了体外感染小鼠脾细胞或纯化的小鼠B淋巴细胞后发生的事件。MHV-68感染可延长小鼠脾细胞活性，刺激细胞增殖。与Epstein-Barr病毒和疱疹病毒Saimiri不同，MHV-68不会引起生长转化。即使当易转化的细胞被感染或选择培养条件以提高细胞的活力时，也不会发生生长转化。在MHV-68感染后，潜伏相关的病毒tRNA被转录。然而，另一个已知的潜伏期相关基因M2的转录没有观察到。此外，无论是通过晚期病毒抗原的特异性抗体染色还是通过早期和晚期mRNAs的原位杂交，都没有证据表明病毒的有效复制。与Epstein-Barr病毒和疱疹病毒Simiri感染的淋巴细胞相比，Gardella凝胶分析表明，体外感染MHV-68的原代淋巴细胞只含有线性病毒DNA。该DNA对核酸酶敏感，表明虽然MHV-68是有效的未包被DNA，但其体外环化效率极低。这些结果从宿主-病毒相互作用的角度进行了讨论。
Primary infection with murine gammaherpesvirus-68 (MHV-68), as with other members of the gammaherpesvirus subfamily, is characterized by a lymphoproliferative phase. MHV-68 causes acute splenomegaly and an infectious mononucleosis-like syndrome in which there is expansion of the CD8(+) T cell subset. In long-term infections, MHV-68 is associated with lymphoma development. In order to elucidate the mechanisms underlying the proliferative processes, the events following infection of murine splenocytes or purified murine B lymphocytes in vitro have been examined. MHV-68 infection prolonged the viability of murine splenocytes and stimulated cellular proliferation. Unlike Epstein-Barr virus and herpesvirus saimiri, MHV-68 did not cause growth transformation. Growth transformation did not occur even when cells with a predisposition to transformation were infected or when culture conditions were selected to enhance the viability of the cells. Following MHV-68 infection, the latency-associated viral tRNAs were transcribed. However, transcription of the other known latency-associated gene, M2, was not observed. In addition, there was no evidence of productive virus replication either by staining with antibodies specific for late virus antigens or by in situ hybridization for early and late mRNAs. In contrast to Epstein-Barr virus- and herpesvirus saimiri-infected lymphocytes, where episomal genomes are seen, Gardella gel analysis indicated that the primary lymphocytes infected by MHV-68 in vitro contained only linear virus DNA. This DNA was nuclease sensitive, indicating that, while MHV-68 was efficiently uncoated, its circularization in vitro was extremely inefficient. These results are discussed in terms of the host-virus interaction.