In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 11 ( 2021-11-22), p. e1010084-
Abstract:
Primary infection with varicella-zoster virus (VZV) causes varicella and the establishment of lifelong latency in sensory ganglion neurons. In one-third of infected individuals VZV reactivates from latency to cause herpes zoster, often complicated by difficult-to-treat chronic pain. Experimental infection of non-human primates with simian varicella virus (SVV) recapitulates most features of human VZV disease, thereby providing the opportunity to study the pathogenesis of varicella and herpes zoster in vivo . However, compared to VZV, the transcriptome and the full coding potential of SVV remains incompletely understood. Here, we performed nanopore direct RNA sequencing to annotate the SVV transcriptome in lytically SVV-infected African green monkey (AGM) and rhesus macaque (RM) kidney epithelial cells. We refined structures of canonical SVV transcripts and uncovered numerous RNA isoforms, splicing events, fusion transcripts and non-coding RNAs, mostly unique to SVV. We verified the expression of canonical and newly identified SVV transcripts in vivo , using lung samples from acutely SVV-infected cynomolgus macaques. Expression of selected transcript isoforms, including those located in the unique left-end of the SVV genome, was confirmed by reverse transcription PCR. Finally, we performed detailed characterization of the SVV homologue of the VZV latency-associated transcript (VLT), located antisense to ORF61. Analogous to VZV VLT, SVV VLT is multiply spliced and numerous isoforms are generated using alternative transcription start sites and extensive splicing. Conversely, low level expression of a single spliced SVV VLT isoform defines in vivo latency. Notably, the genomic location of VLT core exons is highly conserved between SVV and VZV. This work thus highlights the complexity of lytic SVV gene expression and provides new insights into the molecular biology underlying lytic and latent SVV infection. The identification of the SVV VLT homolog further underlines the value of the SVV non-human primate model to develop new strategies for prevention of herpes zoster.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010084
DOI:
10.1371/journal.ppat.1010084.g001
DOI:
10.1371/journal.ppat.1010084.g002
DOI:
10.1371/journal.ppat.1010084.g003
DOI:
10.1371/journal.ppat.1010084.g004
DOI:
10.1371/journal.ppat.1010084.g005
DOI:
10.1371/journal.ppat.1010084.g006
DOI:
10.1371/journal.ppat.1010084.g007
DOI:
10.1371/journal.ppat.1010084.g008
DOI:
10.1371/journal.ppat.1010084.g009
DOI:
10.1371/journal.ppat.1010084.g010
DOI:
10.1371/journal.ppat.1010084.s001
DOI:
10.1371/journal.ppat.1010084.s002
DOI:
10.1371/journal.ppat.1010084.s003
DOI:
10.1371/journal.ppat.1010084.s004
DOI:
10.1371/journal.ppat.1010084.s005
DOI:
10.1371/journal.ppat.1010084.s006
DOI:
10.1371/journal.ppat.1010084.s007
DOI:
10.1371/journal.ppat.1010084.s008
DOI:
10.1371/journal.ppat.1010084.s009
DOI:
10.1371/journal.ppat.1010084.s010
DOI:
10.1371/journal.ppat.1010084.s011
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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