Abstract
Varicella-zoster virus (VZV) persists in ganglia of >90% adults worldwide, reactivating in one-third to cause debilitating shingles. How VZV maintains latency remains unclear. Ultra-deep virus-enriched RNA sequencing of latently infected human trigeminal ganglia (TG) demonstrated consistent expression of a novel spliced VZV mRNA, partially antisense to VZV open reading frame 61 (ORF61). This VZV latency transcript (VLT) is expressed in human TG neurons and encodes a protein with late kinetics in productively infected cells in vitro and in shingles skin lesions. VLT but not the encoded protein represses expression of the viral transcriptional regulator ORF61 and inhibits productive viral infection. The unique characteristics of VLT can be exploited to develop novel intervention strategies aimed at preventing VZV latency and reactivation.
One sentence summary VZV latency is characterized by expression of a novel spliced protein-coding mRNA that represses ORF61 expression and inhibits lytic infection.