Recurrent lymphocytic meningitis (RLM), also referred to as Mollaret’s meningitis is a rare neuro-disease characterized mainly by reactivation of herpes simplex virus (HSV)-2 from sensory ganglia. However, the underlying host immune determinants and viral factors rendering some individuals unable to maintain HSV-2 latency are largely unknown. We collected a cohort of fifteen patients diagnosed with Mollaret’s meningitis. By whole exome sequencing we identified rare host genetic variants predicted to be deleterious in molecules involved in i) ubiquitin-proteasome pathways, ii) the autophagy machinery, and iii) cell proliferation/apoptosis. Moreover, infection of patient cells with HSV-2 or stimulation by virus-derived dsDNA ligands revealed reduced antiviral interferon (IFN) responses in most patients. These findings may contribute to a better understanding of disease pathogenesis and protective immunity to HSV in the central nervous system (CNS), and may ultimately be of importance for identification of therapeutic targets for development of improved prophylaxis and treatment of this disease.

中文翻译：

---

复发性 HSV-2 淋巴细胞性 Mollaret 脑膜炎患者的全外显子组测序。

复发性淋巴细胞性脑膜炎 (RLM)，也称为 Mollaret 脑膜炎，是一种罕见的神经疾病，其主要特征是感觉神经节中单纯疱疹病毒 (HSV)-2 的再激活。然而，导致一些个体无法维持 HSV-2 潜伏期的潜在宿主免疫决定因素和病毒因素在很大程度上是未知的。我们收集了 15 名被诊断患有 Mollaret 脑膜炎的患者。通过全外显子组测序，我们确定了罕见的宿主遗传变异，这些变异预测在参与 i) 泛素-蛋白酶体途径、ii) 自噬机制和 iii) 细胞增殖/凋亡的分子中是有害的。此外，用 HSV-2 感染患者细胞或通过病毒衍生的 dsDNA 配体刺激显示大多数患者的抗病毒干扰素 (IFN) 反应降低。