3 years ago

Varicella Zoster virus expresses multiple small non-coding RNAs.

Markus, Ojha, Golani, Kinchington, Borodiansky-Shteinberg, Goldstein
Many herpesviruses express small non coding RNAs (sncRNA), including microRNAs (miR), that may play roles in regulating lytic and latent infections. None have yet been reported in varicella zoster virus (VZV, HHV-3). Here we analyzed next generation sequencing (NGS) data for small RNAs in VZV-infected fibroblasts and human embryonic stem cell-derived (hESC) neurons. Two independent bioinformatics analyses identified more than 20 VZV-encoded 20-24 nucleotide RNAs, some of which are predicted to have stem-loop precursors potentially representing miRs. These sequences are perfectly conserved between viruses from three clades of VZV. One NGS-identified sequence common to both bioinformatics analyses mapped to the repeat regions of the VZV genome, upstream of the predicted promoter of the immediate-early gene ORF63. This miR candidate was detected in each of 3 independent biological repetitions of NGS of RNA from fibroblasts and neurons productively infected with VZV using Taqman qPCR. Importantly, transfected synthetic RNA oligonucleotides antagonistic to the miR candidate significantly enhanced VZV plaque growth rates. The presence of 6 additional small non-coding RNAs was also verified by Taqman qPCR in productively infected fibroblasts and ARPE19 cells. Our results show that VZV, like other human herpesviruses, encodes several sncRNAs and miR, and some may regulate infection of host cells.Importance Varicella zoster virus is an important human pathogen, with herpes zoster being a major health issue in the aging and immune compromised populations. Small non coding RNAs (sncRNA) are recognized as important actors in modulating gene expression, and this study demonstrates the first reported VZV encoded sncRNAs. Many are clustered to a small genomic region, as seen in other human herpesviruses. At least one VZV sncRNA was expressed in productive infection of neurons and fibroblasts that is likely to reduce viral replication. Since sncRNAs have been suggested to be potential targets for antiviral therapies, identification of these molecules in VZV may provide a new direction for development of treatments for painful herpes zoster.

Publisher URL: http://doi.org/10.1128/JVI.01710-17

DOI: 10.1128/JVI.01710-17

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