TY  - JOUR
A1  - Lodha, Manivel
A1  - Muchsin, Ihsan
A1  - Jürges, Christopher
A1  - Juranic Lisnic, Vanda
A1  - L’Hernault, Anne
A1  - Rutkowski, Andrzej J.
A1  - Prusty, Bhupesh K.
A1  - Grothey, Arnhild
A1  - Milic, Andrea
A1  - Hennig, Thomas
A1  - Jonjic, Stipan
A1  - Friedel, Caroline C.
A1  - Erhard, Florian
A1  - Dölken, Lars
T1  - Decoding murine cytomegalovirus
JF  - PLOS Pathogens
N2  - The genomes of both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) were first sequenced over 20 years ago. Similar to HCMV, the MCMV genome had initially been proposed to harbor ≈170 open reading frames (ORFs). More recently, omics approaches revealed HCMV gene expression to be substantially more complex comprising several hundred viral ORFs. Here, we provide a state-of-the art reannotation of lytic MCMV gene expression based on integrative analysis of a large set of omics data. Our data reveal 365 viral transcription start sites (TiSS) that give rise to 380 and 454 viral transcripts and ORFs, respectively. The latter include 200 small ORFs, some of which represented the most highly expressed viral gene products. By combining TiSS profiling with metabolic RNA labelling and chemical nucleotide conversion sequencing (dSLAM-seq), we provide a detailed picture of the expression kinetics of viral transcription. This not only resulted in the identification of a novel MCMV immediate early transcript encoding the m166.5 ORF, which we termed ie4, but also revealed a group of well-expressed viral transcripts that are induced later than canonical true late genes and contain an initiator element (Inr) but no TATA- or TATT-box in their core promoters. We show that viral upstream ORFs (uORFs) tune gene expression of longer viral ORFs expressed in cis at translational level. Finally, we identify a truncated isoform of the viral NK-cell immune evasin m145 arising from a viral TiSS downstream of the canonical m145 mRNA. Despite being ≈5-fold more abundantly expressed than the canonical m145 protein it was not required for downregulating the NK cell ligand, MULT-I. In summary, our work will pave the way for future mechanistic studies on previously unknown cytomegalovirus gene products in an important virus animal model.
KW  - virology
KW  - genetics
KW  - molecular biology
KW  - immunology
KW  - microbiology
KW  - parasitology
KW  - murine cytomegalovirus (MCMV)
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350480
SN  - 1553-7374
VL  - 19
IS  - 5
ER  - 
TY  - JOUR
A1  - Goettsch, Winfried
A1  - Beerenwinkel, Niko
A1  - Deng, Li
A1  - Dölken, Lars
A1  - Dutilh, Bas E.
A1  - Erhard, Florian
A1  - Kaderali, Lars
A1  - Kleist, Max von
A1  - Marquet, Roland
A1  - Matthijnssens, Jelle
A1  - McCallin, Shawna
A1  - McMahon, Dino
A1  - Rattei, Thomas
A1  - Van Rij, Ronald P.
A1  - Robertson, David L.
A1  - Schwemmle, Martin
A1  - Stern-Ginossar, Noam
A1  - Marz, Manja
T1  - ITN—VIROINF: Understanding (harmful) virus-host interactions by linking virology and bioinformatics
JF  - Viruses
N2  - Many recent studies highlight the fundamental importance of viruses. Besides their important role as human and animal pathogens, their beneficial, commensal or harmful functions are poorly understood. By developing and applying tailored bioinformatical tools in important virological models, the Marie Skłodowska-Curie Initiative International Training Network VIROINF will provide a better understanding of viruses and the interaction with their hosts. This will open the door to validate methods of improving viral growth, morphogenesis and development, as well as to control strategies against unwanted microorganisms. The key feature of VIROINF is its interdisciplinary nature, which brings together virologists and bioinformaticians to achieve common goals.
KW  - bioinformatic
KW  - virus
KW  - virology
KW  - virus host interaction
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236687
SN  - 1999-4915
VL  - 13
IS  - 5
ER  -