Human inborn errors of immunity to herpes viruses

Abstract

Infections with any of the nine human herpes viruses (HHV) can be asymptomatic or lifethreatening. 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 Tcell 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 HSV-1 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-

Twelve Children with Varicella Vaccine Meningitis: Neuropathogenesis of Reactivated Live Attenuated Varicella Vaccine Virus

“…RNA polymerase III is a sensor of foreign DNA in the cytosol (for example, VZV DNA); in that role, the RNA polymerase has been described as a gatekeeper to prevent serious VZV infections [ 57 ]. Because detection of these alleles in the human genome usually requires whole exome sequencing, the prevalence of the inborn errors of immunity in children among the general population is not yet known [ 58 ]. We encourage whole exome sequencing studies on future cases of varicella vaccine meningitis in immunocompetent children.…”

A case of recurrent herpes simplex 2 encephalitis, VZV reactivations, and dominant partial interferon-gamma-receptor-1 deficiency supports relevance of IFNgamma for antiviral defense in humans

“…Whole exome sequencing (WES) of the patient, his wife and the clinically affected son did not reveal any potential causative variation other than IFNɣR1 deficiency. Jouanguy et al recently published inborn errors of human antiviral immunity to herpes viruses [10]. All genes listed by Jouanguy et al (Table 1 [10]) were unaffected as determined by WES.…”

“…Jouanguy et al recently published inborn errors of human antiviral immunity to herpes viruses [10]. All genes listed by Jouanguy et al (Table 1 [10]) were unaffected as determined by WES.…”

An overview of viral infections of the nervous system in the immunosuppressed

“…The typical clinical features of HSE are well recognised with predominant involvement of the fronto-temporal brain regions. It should also be mentioned that immunodeficiencies involving the Toll-like receptor 3 (TLR3) pathway are well established, at least in children, to predispose to HSE [12]. Children with this immune defect are also likely to have relapses of HSE [13].…”