Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Virology. 2010 May 10;400(2):248-58. doi: 10.1016/j.virol.2010.02.013. Epub 2010 Mar 2.
Resistance to lethal encephalitis in mice infected with HSV-1 via the oral mucosa is mouse strain dependent. In susceptible BALB/c, HSV-1 spreads throughout the CNS but in resistant BL/6 mice, virus is restricted to the brainstem. To examine the contribution of cellular immunity in restricting viral spread, we used a combination of antibody depleted and KO mice. Individually, NK/NKT, iNKT, CD4(+), CD8(+), and gammadelta T-cells do not restrict HSV-1 spread. In contrast, virus spreads throughout the CNS of BL/6 CL I KO mice and BL/6 mice treated with either anti-asialoGM1 Ab or both anti-CD8 and anti-NK1.1 mAbs. The results highlight the importance of redundancy in the immune system in restricting viral spread in the CNS, argue for a role of NK/NKT and CD8(+) T-cells in mediating the restriction, and provide a hierarchical order of the individual elements in controlling virus in BL/6 mice infected with HSV-1 via the oral mucosa.
通过口腔黏膜感染 HSV-1 的小鼠对致死性脑炎的抵抗力取决于小鼠品系。在易感的 BALB/c 小鼠中，HSV-1 会在中枢神经系统中传播，但在抵抗性的 BL/6 小鼠中，病毒仅限于脑干。为了研究细胞免疫在限制病毒传播中的作用，我们使用了抗体耗尽和 KO 小鼠的组合。单独的 NK/NKT、iNKT、CD4(+)、CD8(+)和 gammadelta T 细胞并不能限制 HSV-1 的传播。相反，病毒会在 BL/6 CL I KO 小鼠和接受抗-asialoGM1 Ab 或抗-CD8 和抗-NK1.1 mAb 处理的 BL/6 小鼠的整个中枢神经系统中传播。这些结果强调了免疫系统在限制中枢神经系统中病毒传播的冗余性的重要性，认为 NK/NKT 和 CD8(+)T 细胞在介导限制方面发挥作用，并为通过口腔黏膜感染 HSV-1 的 BL/6 小鼠中控制病毒的各个因素提供了一个层次顺序。
