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

• DOI: 10.1038/s41467-018-03569-2
• Publication Date: 2018-03-15T11:53:41Z
• Authors: Daniel P. Depledge; Werner J. D. Ouwe...; Tomohiko Sadaoka; Shirley E. Braspe...; Yasuko Mori; Randall J. Cohrs; Georges M. G. M. ...; Judith Breuer
• Keywords: Varicella zoster virus; Virus latency; Shingles; Pseudorabies; Lytic cycle

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