Journal article
Conserved Herpesvirus Kinase ORF36 Activates B2 Retrotransposons during Murine Gammaherpesvirus Infection
Journal of virology, Vol.94(14), e00262-20
07/01/2020
DOI: 10.1128/JVI.00262-20
PMCID: PMC7343202
PMID: 32404524
Abstract
Short interspersed nuclear elements (SINEs) are RNA polymerase III (RNAPIII)-transcribed, retrotransposable noncoding RNA (ncRNA) elements ubiquitously spread throughout mammalian genomes. While normally silenced in healthy somatic tissue, SINEs can be induced during infection with DNA viruses, including the model murine gammaherpesvirus 68 (MHV68). Here, we explored the mechanisms underlying MHV68 activation of SINE ncRNAs. We demonstrate that lytic MHV68 infection of B cells, macrophages, and fibroblasts leads to robust activation of the B2 family of SINEs in a cell-autonomous manner. B2 ncRNA induction requires neither host innate immune signaling factors nor involvement of the RNAPIII master regulator Maf1. However, we identified MHV68 ORF36, the conserved herpesviral kinase, as playing a key role in B2 induction during lytic infection. SINE activation is linked to ORF36 kinase activity and can also be induced by inhibition of histone deacetylases 1 and 2 (HCAC 1/2), which is one of the known ORF36 functions. Collectively, our data suggest that ORF36-mediated changes in chromatin modification contribute to B2 activation during MHV68 infection and that this activity is conserved in other herpesviral protein kinase homologs.
Viral infection dramatically changes the levels of many types of RNA in a cell. In particular, certain oncogenic viruses activate expression of repetitive genes called retrotransposons, which are normally silenced due to their ability to copy and spread throughout the genome. Here, we established that infection with the gammaherpesvirus MHV68 leads to a dramatic induction of a class of noncoding retrotransposons called B2 SINEs in multiple cell types. We then explored how MHV68 activates B2 SINEs, revealing a role for the conserved herpesviral protein kinase ORF36. Both ORF36 kinase-dependent and kinase-independent functions contribute to B2 induction, perhaps through ORF36 targeting of proteins involved in controlling the accessibility of chromatin surrounding SINE loci. Understanding the features underlying induction of these elements following MHV68 infection should provide insight into core elements of SINE regulation, as well as disregulation of SINE elements associated with disease.
Details
- Title: Subtitle
- Conserved Herpesvirus Kinase ORF36 Activates B2 Retrotransposons during Murine Gammaherpesvirus Infection
- Creators
- Aaron M Schaller - University of California, BerkeleyJessica Tucker - University of California, BerkeleyIan Willis - Albert Einstein College of MedicineBritt A Glaunsinger - University of California, Berkeley
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.94(14), e00262-20
- DOI
- 10.1128/JVI.00262-20
- PMID
- 32404524
- PMCID
- PMC7343202
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Grant note
- R01 CA136367 / NCI NIH HHS R01 AI122528 / NIAID NIH HHS Howard Hughes Medical Institute R21 AI147183 / NIAID NIH HHS
- Language
- English
- Date published
- 07/01/2020
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297437702771
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