Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR-1163, Paris, EU, France; Paris Descartes University, Imagine Institute, Paris, EU, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, USA.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR-1163, Paris, EU, France; Paris Descartes University, Imagine Institute, Paris, EU, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, USA.
Curr Opin Immunol. 2020 Feb;62:106-122. doi: 10.1016/j.coi.2020.01.004. Epub 2020 Jan 31.
Infections with any of the nine human herpes viruses (HHV) can be asymptomatic or life-threatening. The study of patients with severe diseases caused by HHVs, in the absence of overt acquired immunodeficiency, has led to the discovery or diagnosis of various inborn errors of immunity. The related inborn errors of adaptive immunity disrupt α/β T-cell rather than B-cell immunity. Affected patients typically develop HHV infections in the context of other infectious diseases. However, this is not always the case, as illustrated by inborn errors of SAP-dependent T-cell immunity to EBV-infected B cells. The related inborn errors of innate immunity disrupt leukocytes other than T and B cells, non-hematopoietic cells, or both. Patients typically develop only a single type of infection due to HHV, although, again, this is not always the case, as illustrated by inborn errors of TLR3 immunity resulting in HSV1 encephalitis in some patients and influenza pneumonitis in others. Most severe HHV infections in otherwise healthy patients remains unexplained. The forward human genetic dissection of isolated and syndromic HHV-driven illnesses will establish the molecular and cellular basis of protective immunity to HHVs, paving the way for novel diagnosis and management strategies.
任何一种人类疱疹病毒（HHV）的感染都可能是无症状的或危及生命的。对由 HHVs 引起的严重疾病患者的研究，在没有明显获得性免疫缺陷的情况下，导致了各种先天性免疫缺陷的发现或诊断。相关的适应性免疫先天性缺陷会破坏α/β T 细胞，而不是 B 细胞免疫。受影响的患者通常在其他传染病的背景下发生 HHV 感染。然而，情况并非总是如此，例如 SAP 依赖性 T 细胞对 EBV 感染的 B 细胞免疫的先天性缺陷就是如此。相关的先天性固有免疫缺陷会破坏 T 和 B 细胞以外的白细胞、非造血细胞或两者。由于 HHV，患者通常只发生一种类型的感染，尽管并非总是如此，例如 TLR3 免疫的先天性缺陷导致一些患者发生单纯疱疹病毒 1 型脑炎，而另一些患者发生流感性肺炎。在其他方面健康的患者中，大多数严重的 HHV 感染仍然无法解释。对孤立和综合征性 HHV 驱动疾病的人类正向遗传剖析将确定 HHVs 保护性免疫的分子和细胞基础，为新的诊断和管理策略铺平道路。
