TY  - JOUR
A1  - Wyler, Emanuel
A1  - Menegatti, Jennifer
A1  - Franke, Vedran
A1  - Kocks, Christine
A1  - Boltengagen, Anastasiya
A1  - Hennig, Thomas
A1  - Theil, Kathrin
A1  - Rutkowski, Andrzej
A1  - Ferrai, Carmelo
A1  - Baer, Laura
A1  - Kermas, Lisa
A1  - Friedel, Caroline
A1  - Rajewsky, Nikolaus
A1  - Akalin, Altuna
A1  - Dölken, Lars
A1  - Grässer, Friedrich
A1  - Landthaler, Markus
T1  - Widespread activation of antisense transcription of the host genome during herpes simplex virus 1 infection
JF  - Genome Biology
N2  - Background
Herpesviruses 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.

Results
Here, 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.

Conclusions
We 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.
KW  - Virology
KW  - Herpes
KW  - Virus
KW  - Antisense
KW  - Transcription
KW  - IncRNA
KW  - ICP4
KW  - BBC3
KW  - NFKB
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173381
VL  - 18
ER  -