Qin Qingsong, Lauver Matthew, Maru Saumya, Lin Eugene, Lukacher Aron E
Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Virology. 2017 Feb;502:198-205. doi: 10.1016/j.virol.2016.12.028. Epub 2017 Jan 5.
Mouse polyomavirus (MuPyV) causes a smoldering persistent infection in immunocompetent mice. To lower MuPyV infection in acutely and persistently infected mice, and study the impact of a temporal reduction in viral loads on the memory CD8 T cell response, we created a recombinant MuPyV in which a loxP sequence was inserted into the A2 strain genome upstream of the early promoter and another loxP sequence was inserted in cis into the intron shared by all three T antigens. Using mice transgenic for tamoxifen-inducible Cre recombinase, we demonstrated that reduction in MuPyV load during persistent infection was associated with differentiation of virus-specific CD8 T cells having a superior recall response. Evidence presented here supports the concept that reduction in viral load during persistent infection can promote differentiation of protective virus-specific memory CD8 T cells in patients at risk for diseases caused by human polyomaviruses.
小鼠多瘤病毒（MuPyV）在免疫功能正常的小鼠中引发一种潜伏性持续感染。为了降低急性和持续性感染小鼠体内的MuPyV感染，并研究病毒载量的暂时降低对记忆性CD8 T细胞反应的影响，我们构建了一种重组MuPyV，其中一个loxP序列插入到早期启动子上游的A2株基因组中，另一个loxP序列顺式插入到所有三种T抗原共有的内含子中。利用对他莫昔芬诱导型Cre重组酶转基因的小鼠，我们证明持续性感染期间MuPyV载量的降低与具有卓越回忆反应的病毒特异性CD8 T细胞的分化有关。此处提供的证据支持这样一种概念，即持续性感染期间病毒载量的降低可促进人类多瘤病毒所致疾病风险患者体内保护性病毒特异性记忆性CD8 T细胞的分化。
