Herpes simplex virus blocks host transcription termination via the bimodal activities of ICP27

Wang, Xiuye; Hennig, Thomas; Whisnant, Adam W.; Erhard, Florian; Prusty, Bhupesh K.; Friedel, Caroline C.; Forouzmand, Elmira; Hu, William; Erber, Luke; Chen, Yue; Sandri‐Goldin, Rozanne M.; Dölken, Lars; Shi, Yongsheng

doi:10.1038/s41467-019-14109-x

Cited by 71 publications

(112 citation statements)

References 64 publications

(88 reference statements)

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“…HSV-1-induced APA changes could be due to changes in PAS selection during transcription and/or selective loss of individual APA isoforms. To distinguish between these mechanistic models, we directly compared our PAS-seq data with nascent RNA sequencing (4sU-seq) data, which provides information on transcription activities [13]. Meta-analyses of 4sU-seq signals in mock or HSV-1infected cells along the genes that showed HSV-1-induced higher usage of upstream PAS (DtoP) revealed two interesting differences.…”

Section: The Relationship Between the Hsv-1-induced Apa Changes And Tmentioning

confidence: 99%

“…We have previously shown that ICP27, when bound to upstream GC-rich sequences, can activate PAS (Fig. 4G) [13]. To test if the GC contents of the different classes of intronic PAS impact ICP27 binding, we took advantage of the ICP27 CLIP-seq dataset that we generated previously [13].…”

Section: Mechanisms For Hsv-1-mediated Apa Regulationmentioning

confidence: 99%

“…RNA-seq data on the subcellular RNA fractions and 4sU-seq data were previously published [13,17]. PAS-seq data have been deposited to the GEO database (GSE151104).…”

Section: Data and Software Availabilitymentioning

confidence: 99%

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Mechanism and consequences of herpes simplex virus 1-mediated regulation of host mRNA alternative polyadenylation

Shi¹,

Yang²,

Liu³

et al. 2020

Preprint

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Eukaryotic gene expression is extensively regulated by cellular stress and pathogen infections. We have previously shown that herpes simplex virus 1 (HSV-1) and several cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) in host genes and that the viral immediate early factor ICP27 plays an important role in HSV-1-induced DoTT. Here, we show that HSV-1 infection also leads to widespread changes in alternative polyadenylation (APA) of host mRNAs. In the majority of cases, polyadenylation shifts to upstream poly(A) sites (PAS), including many intronic PAS. Mechanistically, ICP27 contributes to HSV-1-mediated APA regulation. HSV-1- and ICP27-induced activation of intronic PAS is sequence-dependent and does not involve general inhibition of U1 snRNP. HSV1-induced intronic polyadenylation is accompanied by early termination of RNAPII. Finally, HSV-1-induced mRNAs polyadenylated at intronic PAS are exported into the cytoplasm while APA isoforms with extended 3’ UTRs are sequestered in the nuclei, both preventing the expression of the full-length gene products. Together with other recent studies, our results suggest that viral infection and cellular stresses induce a multi-faceted host shutoff response that includes DoTT and changes in APA profiles.

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Section: The Relationship Between the Hsv-1-induced Apa Changes And Tmentioning

confidence: 99%

Section: Mechanisms For Hsv-1-mediated Apa Regulationmentioning

confidence: 99%

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Mechanism and consequences of herpes simplex virus 1-mediated regulation of host mRNA alternative polyadenylation

Shi¹,

Yang²,

Liu³

et al. 2020

Preprint

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“…The HSV IE gene product ICP4 acts as a major transcriptional activator that is essential to regulate viral E and L genes. ICP27 promotes viral infection through splicing, processing, and mRNA export [ 17 ]. The present study explored CyHV-2 IE genes through high-throughput sequencing combined with the use of inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Immediate-Early Genes of Cyprinid Herpesvirus 2

Tang

Wang³

et al. 2020

Viruses

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Cyprinid herpesvirus 2 (CyHV-2), which infects goldfish and crucian carp causing high mortality, is an emerging viral pathogen worldwide. The genome of CyHV-2 is large and comprises double-stranded DNA, including several genes similar to cyprinid herpesvirus 1, ictalurid herpesvirus-1, cyprinid herpesvirus 3, and ranid herpesvirus-1. Genes of DNA viruses are expressed in three temporal phases: immediate-early (IE), early (E), and late (L) genes. Viral IE genes initiate transcription as soon as the virus enters the host, without viral DNA replication. IE gene products enable the efficient expression of E and L genes or regulate the host to initiate virus replication. In the present study, five IE genes of CyHV-2 were identified, including open reading frame (ORF)54, ORF121, ORF141, ORF147, and ORF155. Time course analysis and reverse transcription polymerase chain reaction confirmed five IE genes, thirty-four E genes, and thirty-nine L genes. In addition, all 150 ORFs identified in the CyHV-2 genome are transcribed, and are expressed in chronological order, similar to other herpesviruses. This study is the first to identify the IE genes of CyHV-2, which will provide more information for viral molecular characterization.

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“…HSV-1 ICP27 was recently shown to block the transcription termination of host genes by inhibiting mRNA 3′ processing. Furthermore, ICP27 can act as a sequence-dependent activator of mRNA 3′ processing to promote efficient transcription termination of viral transcripts, indicating that HSV-1 ICP27 plays an important role in host shutoff [27].…”

Section: Main Textmentioning

confidence: 99%

Host shutoff activity of VHS and SOX-like proteins: role in viral survival and immune evasion

Wang

Cheng

et al. 2020

Virol J

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Background: Host shutoff refers to the widespread downregulation of host gene expression and has emerged as a key process that facilitates the reallocation of cellular resources for viral replication and evasion of host antiviral immune responses. Main body: The Herpesviridae family uses a number of proteins that are responsible for host shutoff by directly targeting messenger RNA (mRNA), including virion host shutoff (VHS) protein and the immediate-early regulatory protein ICP27 of herpes simplex virus types 1 (HSV-1) and the SOX (shutoff and exonuclease) protein and its homologs in Gammaherpesvirinae subfamilies, although these proteins are not homologous. In this review, we highlight evidence that host shutoff is promoted by the VHS, ICP27 and SOX-like proteins and that they also contribute to immune evasion. Conclusions: Further studies regarding the host shutoff proteins will not only contribute to provide new insights into the viral replication, expression and host immune evasion process, but also provide new molecular targets for the development of antiviral drugs and therapies.

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Herpes simplex virus blocks host transcription termination via the bimodal activities of ICP27

Cited by 71 publications

References 64 publications

Mechanism and consequences of herpes simplex virus 1-mediated regulation of host mRNA alternative polyadenylation

Mechanism and consequences of herpes simplex virus 1-mediated regulation of host mRNA alternative polyadenylation

Identification of the Immediate-Early Genes of Cyprinid Herpesvirus 2

Host shutoff activity of VHS and SOX-like proteins: role in viral survival and immune evasion

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