潜伏性、早期或晚期人类疱疹病毒-6B 在成人内侧颞叶癫痫中的表达：病毒生命周期与脑组织和脑脊液中炎症细胞因子的关联。
Latent, Early or Late Human Herpes Virus-6B Expression in Adult Mesial Temporal Lobe Epilepsy: Association of Virus Life Cycle with Inflammatory Cytokines in Brain Tissue and Cerebral Spinal Fluid.
机构信息
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
University of Electronic Science and Technology of China Hospital, China.
出版信息
Neuroscience. 2022 Nov 10;504:21-32. doi: 10.1016/j.neuroscience.2022.08.021. Epub 2022 Sep 5.
BACKGROUND
Human herpes virus-6B (HHV-6B) was suggested as an important etiologic factor of mesial temporal lobe epilepsy, while the mechanism is still unknown. Here, we aimed to analyze antigens representing latent, early and late HHV-6B infection and the association with inflammatory cytokines in brain tissue and cerebral spinal fluid (CSF) from MTLE patients with HHV-6B-positivity.
METHODS
Nested polymerase chain reaction (nPCR), real-time PCR, immunohistochemistry (IHC) and suspension bead array for cytokines were performed.
RESULTS
Nested polymerase chain reaction (nPCR) in brain tissue revealed HHV-6B DNA in 19 of 49 MTLE patients (39%) and 1 of 19 controls (5%) (P < 0.001), but not in CSF. ICH showed HHV-6B early antigen (P41) positivity in 3 patients (6%), late antigen (gp116/54/64) positivity in 5 patients (10%), latent antigen (U94) positivity in 8 patients (16%), and multiple antigen (early and late or/and latent) positivity in 9 patients (18%). None of these HHV-6B related proteins were found positive in control brain tissue. PCR revealed significant up-regulation of IL-1a, IL-2 and IL-7 mRNA levels in the brain tissue from MTLE patients expressing early antigens compared to those expressing late, latent, multiple antigens, negative antigens and the controls. Suspension bead array of the CSF confirmed significant up-regulation of IL-1a and IL-7 protein expression from MTLE patients expressing early antigens compared to the other groups.
CONCLUSIONS
Our finding suggests HHV-6B is a common etiologic agent of MTLE. Different virus life cycle may play an important modifying role in inflammatory biology that warrants further investigation. Though virus DNA is difficult detected in CSF, up-regulation of IL-1a and IL-7 in CSF indicates the two cytokines may be taken as indirect biomarker of HHV-6B infection.
背景
人类疱疹病毒-6B（HHV-6B）被认为是内侧颞叶癫痫的重要病因，但机制尚不清楚。在这里，我们旨在分析代表潜伏、早期和晚期 HHV-6B 感染的抗原，并分析其与 HHV-6B 阳性的内侧颞叶癫痫患者脑组织和脑脊液（CSF）中炎症细胞因子的关系。
方法
采用巢式聚合酶链反应（nPCR）、实时 PCR、免疫组织化学（IHC）和细胞因子悬浮珠阵列法进行检测。
结果
脑组织 nPCR 显示 49 例内侧颞叶癫痫患者中有 19 例（39%）和 19 例对照中有 1 例（5%）（P < 0.001）存在 HHV-6B DNA，但在 CSF 中不存在。IHC 显示 3 例（6%）患者存在 HHV-6B 早期抗原（P41）阳性，5 例（10%）患者存在晚期抗原（gp116/54/64）阳性，8 例（16%）患者存在潜伏抗原（U94）阳性，9 例（18%）患者存在多种抗原（早期和晚期或/和潜伏）阳性。这些 HHV-6B 相关蛋白在对照脑组织中均未发现阳性。PCR 显示，与表达晚期、潜伏、多种抗原、阴性抗原和对照组的患者相比，表达早期抗原的内侧颞叶癫痫患者脑组织中 IL-1a、IL-2 和 IL-7 mRNA 水平显著上调。CSF 悬浮珠阵列分析证实，与其他组相比，表达早期抗原的内侧颞叶癫痫患者的 CSF 中 IL-1a 和 IL-7 蛋白表达水平显著上调。
结论
我们的研究结果表明，HHV-6B 是内侧颞叶癫痫的常见病因。不同的病毒生命周期可能在炎症生物学中发挥重要的修饰作用，值得进一步研究。尽管 CSF 中难以检测到病毒 DNA，但 CSF 中 IL-1a 和 IL-7 的上调表明这两种细胞因子可能作为 HHV-6B 感染的间接生物标志物。
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