Stewart J P, Usherwood E J, Ross A, Dyson H, Nash T
Department of Veterinary Pathology, The University of Edinburgh, Edinburgh EH9 1QH, United Kingdom.
J Exp Med. 1998 Jun 15;187(12):1941-51. doi: 10.1084/jem.187.12.1941.
It is currently believed that latently infected, resting B lymphocytes are central to gammaherpesvirus persistence, whereas mucosal epithelial cells are considered nonessential. We have readdressed the question of nonlymphoid persistence using murine gammaherpesvirus 68 (MHV-68). To dissect lymphoid from nonlymphoid persistence, we used microMT transgenic mice that are defective in B cells. MHV-68 DNA persisted in the lungs of intact and B cell-deficient mice. Both episomal and linear forms of the virus genome were present in lungs, implying the presence of both latency and productive replication. In situ hybridization for virus tRNA transcripts revealed latent MHV-68 in pulmonary epithelial cells. Infectious virus was recovered from the lungs of microMT mice after T cell depletion, showing that the persisting virus DNA was reactivatable. Finally, using adoptive transfer of B cells into B cell-deficient mice, it was shown that virus persisting in lungs seeded splenic B cells, and virus resident in the spleen seeded the lungs. These results show that mucosal epithelia can act as a nonlymphoid reservoir for gammaherpesvirus persistence, and that there is a two-way movement of virus between lymphoid and nonlymphoid compartments during persistence.
目前认为，潜伏感染的静止B淋巴细胞是γ疱疹病毒持续存在的核心，而黏膜上皮细胞被认为并非必需。我们利用小鼠γ疱疹病毒68（MHV - 68）重新探讨了非淋巴细胞持续存在的问题。为了区分淋巴细胞与非淋巴细胞的持续存在情况，我们使用了B细胞存在缺陷的microMT转基因小鼠。MHV - 68 DNA在完整小鼠和B细胞缺陷小鼠的肺中持续存在。病毒基因组的游离型和线性形式均存在于肺中，这意味着存在潜伏和活跃复制。病毒tRNA转录本的原位杂交显示肺上皮细胞中有潜伏的MHV - 68。T细胞耗竭后，从microMT小鼠的肺中回收了感染性病毒，表明持续存在的病毒DNA是可激活的。最后，通过将B细胞过继转移到B细胞缺陷小鼠中，发现肺中持续存在的病毒接种到脾脏B细胞，而脾脏中的病毒接种到肺中。这些结果表明，黏膜上皮可作为γ疱疹病毒持续存在的非淋巴细胞储存库，并且在持续存在期间病毒在淋巴细胞和非淋巴细胞区室之间存在双向移动。
