A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61.

Daniel P Depledge, Werner J D Ouwendijk, Tomohiko Sadaoka, Shirley E Braspenning, Yasuko Mori, Randall J Cohrs, Georges M G M Verjans, Judith Breuer

Nature communications 2018 Mar 21

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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.

Citation

Daniel P Depledge, Werner J D Ouwendijk, Tomohiko Sadaoka, Shirley E Braspenning, Yasuko Mori, Randall J Cohrs, Georges M G M Verjans, Judith Breuer. A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61. Nature communications. 2018 Mar 21;9(1):1167