Varicella-zoster virus (VZV) is a double-stranded DNA virus belonging to the Herpesviridae family that causes chickenpox upon primary infection. It establishes latency in the ganglia and can reactivate as herpes zoster when immunity declines, although it generally confers lifelong immunity. Recurrent or severe disseminated herpes zoster may indicate an underlying immunodeficiency. The patient was a 19-year-old man with a history of five episodes of chickenpox in childhood. He developed Kaposi’s varicelliform eruption with headache and was treated with acyclovir after PCR of the cerebrospinal fluid was positive for VZV. Whole-exome sequencing revealed a splice-site variant in POLR3F (c.249-2A>G). In a viral infection model using peripheral blood mononuclear cells with intracellular transfection of fragmented nucleic acids, the expression of IFN-α and IFN-β was markedly reduced compared with that in healthy controls. POLR3F encodes a subunit of RNA polymerase III (Pol III), which transcribes tRNA and is ubiquitously expressed, including immune cells. Heterozygous variants in genes encoding Pol III subunits have been reported to cause severe VZV infection; however, the c.249-2A>G variant is novel. Immunological investigation of this condition may provide insights not only into the immune response to VZV infection but also into the mechanisms of host defense against DNA viruses and the development of therapeutic strategies.
