Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Center for Molecular Medicine, Stockholm, Sweden.
Scand J Immunol. 2020 Dec;92(6):e12984. doi: 10.1111/sji.12984. Epub 2020 Oct 23.
Human herpesvirus 6A (HHV-6A) and 6B (HHV-6B) are two closely related viruses that can infect cells of the central nervous system (CNS). The similarities between these viruses have made it difficult to separate them on serological level. The broad term HHV-6 remains when referring to studies where the two species were not distinguished, and as such, the seroprevalence is over 90% in the adult population. HHV-6B has been detected in up to 100% of infants with the primary infection roseola infantum, but less is known about the primary infection of HHV-6A. Both viruses are neurotropic and have capacity to establish lifelong latency in cells of the central nervous system, with potential to reactivate and cause complications later in life. HHV-6A infection has been associated with an increased risk of multiple sclerosis (MS), whereas HHV-6B is indicated to be involved in pathogenesis of epilepsy. These two associations show how neurological diseases might be caused by viral infections, but as suggested here, through completely different molecular mechanisms, in an autoimmune disease, such as MS, by triggering an overreaction of the immune system and in epilepsy by hampering internal cellular functions when the immune system fails to eliminate the virus. Understanding the viral mechanisms of primary infection and reactivation and their spectrum of associated symptoms will aid our ability to diagnose, treat and prevent these severe and chronic diseases. This review explores the role of HHV-6A and HHV-6B specifically in MS and epilepsy, the evidence to date and the future directions of this field.
人类疱疹病毒 6A（HHV-6A）和 6B（HHV-6B）是两种密切相关的病毒，可以感染中枢神经系统（CNS）的细胞。这些病毒之间的相似性使得在血清学水平上难以将它们区分开来。当涉及到未区分两种病毒的研究时，使用广义术语 HHV-6，因此，成年人中的血清流行率超过 90%。在原发性感染幼儿急疹的婴儿中，已经检测到高达 100%的 HHV-6B，但对 HHV-6A 的原发性感染知之甚少。这两种病毒都具有神经嗜性，并具有在中枢神经系统细胞中建立终身潜伏的能力，有重新激活并在以后的生活中引起并发症的潜力。HHV-6A 感染与多发性硬化症（MS）的风险增加有关，而 HHV-6B 则表明与癫痫的发病机制有关。这两个关联表明，神经疾病可能是由病毒感染引起的，但正如这里所建议的那样，通过完全不同的分子机制，在自身免疫性疾病（如 MS）中，通过触发免疫系统的过度反应，在癫痫中，通过在免疫系统未能消除病毒时干扰内部细胞功能，导致疾病发生。了解原发性感染和重新激活的病毒机制及其相关症状谱将有助于我们诊断、治疗和预防这些严重和慢性疾病的能力。这篇综述探讨了 HHV-6A 和 HHV-6B 在多发性硬化症和癫痫中的具体作用、迄今为止的证据以及该领域的未来方向。
