John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
Present address: Department of Microbial Sciences, University of Surrey, Guildford, UK.
J Gen Virol. 2018 May;99(5):682-692. doi: 10.1099/jgv.0.001059. Epub 2018 Apr 5.
CD8 T cells have a role in the control of acute herpes simplex virus (HSV) infection and may also be important in the maintenance of latency. In this study we have explored the consequences of boosting the efficacy of CD8 T cells against HSV by increasing the amount of an MHC I-presented epitope on the surface of infected cells. To do this we used HSVs engineered to express an extra copy of the immunodominant CD8 T cell epitope in C57Bl/6 mice, namely gB498 (SSIEFARL). Despite greater presentation of gB498 on infected cells, CD8 T cell responses to these viruses in mice were similar to those elicited by a control virus. Further, the expression of extra gB498 did not significantly alter the extent or stability of latency in our mouse model, and virus loads in skin and sensory ganglia of infected mice were not affected. Surprisingly, mice infected with these viruses developed significantly larger skin lesions than those infected with control viruses and notably, this phenotype was dependent on MHC haplotype. Therefore increasing the visibility of HSV-infected cells to CD8 T cell attack did not impact neural infection or latency, but rather enhanced pathology in the skin.
CD8 T 细胞在控制急性单纯疱疹病毒（HSV）感染中起作用，并且在潜伏期维持中也可能很重要。在这项研究中，我们通过增加感染细胞表面 MHC I 呈递表位的数量来探索增强 CD8 T 细胞对 HSV 效力的后果。为此，我们使用了在 C57Bl/6 小鼠中表达免疫显性 CD8 T 细胞表位的额外拷贝的 HSV 进行工程改造，即 gB498（SSIEFARL）。尽管感染细胞上 gB498 的呈递增加了，但这些病毒在小鼠中引起的 CD8 T 细胞反应与对照病毒引起的反应相似。此外，额外 gB498 的表达并未显著改变我们小鼠模型中潜伏期的程度或稳定性，并且感染小鼠的皮肤和感觉神经节中的病毒载量也未受到影响。令人惊讶的是，感染这些病毒的小鼠比感染对照病毒的小鼠形成了明显更大的皮肤损伤，并且这种表型依赖于 MHC 单倍型。因此，增加 HSV 感染细胞对 CD8 T 细胞攻击的可见性不会影响神经感染或潜伏期，但会增强皮肤的病理学。
