Henipaviruses and lyssaviruses target nucleolar treacle protein and regulate ribosomal RNA synthesis |
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Authors: | Stephen M. Rawlinson Tianyue Zhao Katie Ardipradja Yilin Zhang Patrick F. Veugelers Jennifer A. Harper Cassandra T. David Vinod Sundaramoorthy Gregory W. Moseley |
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Affiliation: | 1. Department of Microbiology, Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia;2. Commonwealth Scientific and Industrial Research Organisation (CSIRO), Australian Centre for Disease Preparedness (ACDP), East Geelong, Victoria, Australia;3. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Australia |
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Abstract: | The nucleolus is a common target of viruses and viral proteins, but for many viruses the functional outcomes and significance of this targeting remains unresolved. Recently, the first intranucleolar function of a protein of a cytoplasmically-replicating negative-sense RNA virus (NSV) was identified, with the finding that the matrix (M) protein of Hendra virus (HeV) (genus Henipavirus, family Paramyxoviridae) interacts with Treacle protein within nucleolar subcompartments and mimics a cellular mechanism of the nucleolar DNA-damage response (DDR) to suppress ribosomal RNA (rRNA) synthesis. Whether other viruses utilise this mechanism has not been examined. We report that sub-nucleolar Treacle targeting and modulation is conserved between M proteins of multiple Henipaviruses, including Nipah virus and other potentially zoonotic viruses. Furthermore, this function is also evident for P3 protein of rabies virus, the prototype virus of a different RNA virus family (Rhabdoviridae), with Treacle depletion in cells also found to impact virus production. These data indicate that unrelated proteins of viruses from different families have independently developed nucleolar/Treacle targeting function, but that modulation of Treacle has distinct effects on infection. Thus, subversion of Treacle may be an important process in infection by diverse NSVs, and so could provide novel targets for antiviral approaches with broad specificity. |
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Keywords: | henipavirus matrix nucleus nucleolus phosphoprotein protein trafficking rabies ribosome biogenesis treacle virus |
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