Varicella-zoster virus (VZV), an alphaherpesvirus, establishes lifelong latent infection in the neurons of >90% humans worldwide, reactivating in one-third to cause shingles, debilitating pain and stroke. How VZV maintains latency remains unclear. Here, using ultra-deep virus-enriched RNA sequencing of latently infected human trigeminal ganglia (TG), we demonstrate the consistent expression of a spliced VZV mRNA, antisense to VZV open reading frame 61 (ORF61). The spliced VZV latency-associated 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. Whereas multiple alternatively spliced VLT isoforms (VLTly) are expressed during lytic infection, a single unique VLT isoform, which specifically suppresses ORF61 gene expression in co-transfected cells, predominates in latently VZV-infected human TG. The discovery of VLT links VZV with the other better characterized human and animal neurotropic alphaherpesviruses and provides insights into VZV latency.,
Nature Communications
Department of Virology

Depledge, D.P. (Daniel P.), Ouwendijk, W., Sadaoka, T. (Tomohiko), Braspenning, S.E. (Shirley E.), Mori, Y. (Yasuko), Cohrs, R., … Breuer, J. (Judith). (2018). A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene. Nature Communications, 9(1). doi:10.1038/s41467-018-03569-2