Widespread activation of antisense transcription of the host genome during herpes simplex virus 1 infection

Abstract

BackgroundHerpesviruses can infect a wide range of animal species. Herpes simplex virus 1 (HSV-1) is one of the eight herpesviruses that can infect humans and is prevalent worldwide. Herpesviruses have evolved multiple ways to adapt the infected cells to their needs, but knowledge about these transcriptional and post-transcriptional modifications is sparse.ResultsHere, we show that HSV-1 induces the expression of about 1000 antisense transcripts from the human host cell genome. A subset of these is also activated by the closely related varicella zoster virus. Antisense transcripts originate either at gene promoters or within the gene body, and they show different susceptibility to the inhibition of early and immediate early viral gene expression. Overexpression of the major viral transcription factor ICP4 is sufficient to turn on a subset of antisense transcripts. Histone marks around transcription start sites of HSV-1-induced and constitutively transcribed antisense transcripts are highly similar, indicating that the genetic loci are already poised to transcribe these novel RNAs. Furthermore, an antisense transcript overlapping with the BBC3 gene (also known as PUMA) transcriptionally silences this potent inducer of apoptosis in cis.ConclusionsWe show for the first time that a virus induces widespread antisense transcription of the host cell genome. We provide evidence that HSV-1 uses this to downregulate a strong inducer of apoptosis. Our findings open new perspectives on global and specific alterations of host cell transcription by viruses.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1329-5) contains supplementary material, which is available to authorized users.

Single-cell RNA-sequencing of Herpes simplex virus 1-infected cells identifies NRF2 activation as an antiviral program

“…3c), showed strong positive correlations with viral transcripts. Similarly, we found that RASD1 and RRAD were up-regulated in previously published microarray, RNA-seq, and ribosome profiling datasets [5,6,30,31], indicating that the induction of these two genes is independent of the cell type and virus strain. To investigate the influence of RASD1 and RRAD on viral production, we depleted RASD1 and RRAD by siRNA knockdown prior to infection ( Fig.…”

“…At 72 hpi, viral supernatant was collected and sterile-filtered through a 0.45 μm pore size filter and stored at −80°C. Viral titers were determined by plaque assay as described previously [5].…”

“…A hallmark of HSV-1 is the way it alters the cellular RNA metabolism and RNA content on many levels. On one hand, viral mechanisms activate transcription of viral genes and interfere with splicing regulation, RNA polymerase II transcription, and RNA stability to inhibit synthesis of cellular proteins [2][3][4][5][6][7][8]. On the other hand, virus entry affects a range of cellular pathways, which may in turn lead to transcriptional activation or repression of downstream target genes [9].…”

Single-cell RNA-sequencing analysis identifies host long noncoding RNA MAMDC2-AS1 as a co-factor for HSV-1 nuclear transport

“…Indeed, lncRNAs play crucial roles in the process of HSV-l infection [14,15]. HSV-1 infection also alters the expression profile from the host cell genome, especially the expression of antisense transcripts [16][17][18][19]. In general, lncRNAs function in viral infection primarily through two manners, one being dependent of the antiviral response by the host and the other being antiviral response-independent, such as cellular metabolism, maintaining the stability of viral factors and facilitating the expression of viral genes [16,[20][21][22][23][24].…”

In vitro antiviral activity of Brazilian Cerrado plant extracts against animal and human herpesviruses

“…The herpes simplex virus (HSV-1) is pathogenic to humans (Wyler et al, 2017), whereas equine (EqHV-1) and swine herpesviruses (SuHV-1), are responsible for causing serious diseases in horses and pigs respectively, resulting in large economic losses (Wernike et al, 2013;Gulati et al, 2016). These viruses belong to the subfamily Alphaherpesvirinae, characterized by a rapid lytic viral cycle and the establishment of neuronal latency, which can be reactivated (Riaz et al, 2017).…”