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Mutations in RNA Polymerase III genes and defective DNA sensing in adults with varicella-zoster virus CNS infection
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Mutations in RNA Polymerase III genes and defective DNA sensing in adults with varicella-zoster virus CNS infection
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Journal Article
Mutations in RNA Polymerase III genes and defective DNA sensing in adults with varicella-zoster virus CNS infection
2019
Overview
Recently, deficiency in the cytosolic DNA sensor RNA Polymerase III was described in children with severe primary varicella-zoster virus (VZV) infection in the CNS and lungs. In the present study we examined adult patients with VZV CNS infection caused by viral reactivation. By whole exome sequencing we identified mutations in POL III genes in two of eight patients. These mutations were located in the coding regions of the subunits POLR3A and POLR3E. In functional assays, we found impaired expression of antiviral and inflammatory cytokines in response to the POL III agonist Poly(dA:dT) as well as increased viral replication in patient cells compared to controls. Altogether, this study provides significant extension on the current knowledge on susceptibility to VZV infection by demonstrating mutations in POL III genes associated with impaired immunological sensing of AT-rich DNA in adult patients with VZV CNS infection.
Publisher
Nature Publishing Group
Subject
