Department of Neurology, Mayo Clinic, Rochester, Minnesota, United States of America.
PLoS One. 2012;7(2):e32767. doi: 10.1371/journal.pone.0032767. Epub 2012 Feb 29.
Recent evidence in multiple sclerosis (MS) suggests that active CMV infection may result in more benign clinical disease. The goal of this pilot study was to determine whether underlying murine CMV (MCMV) infection affects the course of the Theiler's murine encephalitis virus (TMEV) induced murine model of MS. A group of eight TMEV-infected mice were co-infected with MCMV at 2 weeks prior to TMEV infection while a second group of TMEV-infected mice received MCMV two weeks post TMEV. We also used 2 control groups, where at the above time points MCMV was replaced with PBS. Outcome measures included (1) monthly monitoring of disability via rotarod for 8 months; (2) in vivo MRI for brain atrophy studies and (3) FACS analysis of brain infiltrating lymphocytes at 8 months post TMEV infection. Co-infection with MCMV influenced the disease course in mice infected prior to TMEV infection. In this group, rotarod detectable motor performance was significantly improved starting 3 months post-infection and beyond (p≤0.024). In addition, their brain atrophy was close to 30% reduced at 8 months, but this was only present as a trend due to low power (p = 0.19). A significant reduction in the proportion of brain infiltrating CD3+ cells was detected in this group (p = 0.026), while the proportion of CD45+ Mac1+ cells significantly increased (p = 0.003). There was also a strong trend for a reduced proportion of CD4+ cells (p = 0.17) while CD8 and B220+ cell proportion did not change. These findings support an immunomodulatory effect of MCMV infection in this MS model. Future studies in this co-infection model will provide insight into mechanisms which modulate the development of demyelination and may be utilized for the development of novel therapeutic strategies.
最近的多发性硬化症（MS）证据表明，活动性 CMV 感染可能导致更良性的临床疾病。本研究的目的是确定潜在的鼠 CMV（MCMV）感染是否会影响 TMEV 诱导的 MS 小鼠模型的病程。一组 8 只 TMEV 感染的小鼠在 TMEV 感染前 2 周感染 MCMV，第二组 TMEV 感染的小鼠在 TMEV 后 2 周感染 MCMV。我们还使用了 2 个对照组，在上述时间点用 PBS 代替 MCMV。结果测量包括（1）通过旋转棒每月监测 8 个月的残疾；（2）脑萎缩研究的体内 MRI；（3）TMEV 感染后 8 个月脑浸润淋巴细胞的 FACS 分析。MCMV 与 TMEV 感染前感染的小鼠共感染影响疾病进程。在该组中，从感染后 3 个月开始，旋转棒检测到的运动表现明显改善（p≤0.024）。此外，他们的脑萎缩在 8 个月时减少了近 30%，但由于功率低，这只是一个趋势（p=0.19）。在该组中检测到脑浸润 CD3+细胞的比例显著降低（p=0.026），而 CD45+Mac1+细胞的比例显著增加（p=0.003）。CD4+细胞的比例也有降低的趋势（p=0.17），而 CD8 和 B220+细胞的比例没有变化。这些发现支持 MCMV 感染在该 MS 模型中的免疫调节作用。在这种共感染模型中的进一步研究将提供关于调节脱髓鞘发展的机制的见解，并可能用于开发新的治疗策略。
