These transcripts map antisense to the gene encoding the conserved multifunctional HSV infected cell protein 0 (ICP0), to which varicella-zoster virus (VZV) open reading frame 61 (ORF61) is homologous, which besides inhibiting intrinsic cellular antiviral responses is the major transcriptional transactivator of lytic viral genes required for reactivation of latent HSV 2– 10. For the best-studied αHVs, including herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), pseudorabies virus and bovine herpesvirus 1 (BHV-1), viral latency has been shown to be accompanied by the expression of a single or restricted set of latency-associated transcripts (LATs) 2– 6. The discovery of VLT links VZV with the other better characterized human and animal neurotropic alphaherpesviruses and provides insights into VZV latency.ĭuring primary infection, neurotropic alphaherpesviruses (αHVs) gain access to neurons in sensory, cranial and autonomic ganglia to establish a lifelong latent infection from which they can reactivate to cause debilitating disease 1. Whereas multiple alternatively spliced VLT isoforms (VLT ly) 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.
#Lonza bluesense skin#
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. 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).
How VZV maintains latency remains unclear. 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. The discovery of VLT links VZV with the other better characterized human and animal neurotropic alphaherpesviruses and provides insights into VZV latency. 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.
0 kommentar(er)
