Antibody to Varicella-Zoster Virus Immediate-Early Protein 62 Augments Allodynia in Zoster via Brain-Derived Neurotrophic Factor
Antibody to Varicella-Zoster Virus Immediate-Early Protein 62 Augments Allodynia in Zoster via Brain-Derived Neurotrophic Factor
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DOI：
10.1128/jvi.02061-09
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发表时间：
2010-02-01
影响因子：
5.4
通讯作者：
Tsumoto, Tadaharu
中科院分区：
文献类型：
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作者：
Hama, Yuka;Shiraki, Kimiyasu;Tsumoto, Tadaharu
水痘带状疱疹病毒 (VZV) 表达立即早期蛋白 62 (IE62)，带状疱疹与神经性疼痛有关。脑源性神经营养因子（BDNF）参与疼痛超敏反应的神经机制。带状疱疹与前驱症状和 VZV 加强抗体的大量产生有关。我们假设鞘内产生的 IE62 抗体与 BDNF 交叉反应以及皮肤损伤造成的神经损伤可能通过增强 BDNF 活性来增强带状疱疹的异常性疼痛。针对 IE62 的 268-556 肽的三种单克隆抗体之一识别 BDNF。检查了 IE62 和 BDNF 之间的免疫交叉反应性以及抗 IE62 单克隆抗体（抗 IE62 MAb）与 BDNF 交叉反应性对培养神经元中 BDNF 活性的影响。抗IE62 MAb和抗BDNF MAb识别IE62的414-429肽和BDNF二聚体。抗 IE62 MAb 显着增强神经元中 BDNF 相关的转录和脊髓背角神经元的形态发育。患者血清可识别 IE62 和 BDNF，并增强神经元中的 BDNF 活性。抗 IE62 抗体对机械性异常性疼痛的作用通过在小鼠脊髓神经损伤 (SNI) 中使用 von Frey 丝的异常性疼痛阈值来表征。对小鼠施用抗 IE62 MAb 或用交叉反应 IE62 蛋白进行免疫显着增强了 SNI 一侧的机械异常性疼痛，但未受伤侧则没有。抗 IE62 抗体增强了 SNI 小鼠神经元中的 BDNF 活性和异常性疼痛。鞘内产生抗 IE62 抗体增强 BDNF 活性和带状疱疹引起的周围神经损伤，可能参与带状疱疹异常性疼痛的发病机制。
Varicella-zoster virus (VZV) expresses immediate-early protein 62 (IE62), and zoster is associated with neuropathic pain. Brain-derived neurotrophic factor (BDNF) is involved in the neuronal mechanism underlying pain hypersensitivity. Zoster is associated with prodrome and the robust production of booster antibody to VZV. We hypothesized that the intrathecal production of antibody to IE62 cross-reacting with BDNF and the nerve injury by skin lesions may augment allodynia in zoster by enhancing BDNF activity. One of three monoclonal antibodies against the 268-556 peptide of IE62 recognized BDNF. Immunological cross-reactivity between IE62 and BDNF and the effects of anti-IE62 monoclonal antibody (anti-IE62 MAb) cross-reactivity with BDNF on BDNF activity in cultured neurons were examined. Anti-IE62 MAb and anti-BDNF MAbs recognized the 414-429 peptide of IE62 and the BDNF dimer. Anti-IE62 MAb significantly augmented BDNF-related transcription in neurons and the morphological development of spinal dorsal horn neurons. Sera from patients recognized IE62 and BDNF and enhanced BDNF activity in neurons. The effect of anti-IE62 antibody on mechanical allodynia was characterized by the threshold of allodynia using von Frey filaments in a spinal nerve injury (SNI) in mice. The administration of anti-IE62 MAb to or immunization with cross-reacting IE62 protein to mice significantly enhanced mechanical allodynia on the side with SNI but not on the uninjured side. Anti-IE62 antibody augmented BDNF activity in neurons and allodynia in mice with SNI. The intrathecal production of anti-IE62 antibody augmenting BDNF activity and peripheral nerve injury by zoster may participate in the pathogenesis of allodynia in zoster.