Determining the molecular drivers of species-specific interferon-stimulated gene product 15 interactions with nairovirus ovarian tumor domain proteases
| Autor: | Brendan T. Freitas, Caroline Langley, Florine E. M. Scholte, Scott D. Pegan, Eric Bergeron, John V. Dzimianski, Isabelle L. Williams, Jessica R. Spengler |
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| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular medicine.medical_treatment Sequence Homology Pathogenesis Pathology and Laboratory Medicine Crystallography X-Ray Database and Informatics Methods Mice Electricity Bats Medicine and Health Sciences Phylogeny Genetics Mammals 0303 health sciences Nairovirus Multidisciplinary Fruit Bats Physics 030302 biochemistry & molecular biology Eukaryota Agriculture Ruminants General Medicine Vertebrates Physical Sciences Host-Pathogen Interactions Medicine Cytokines General Agricultural and Biological Sciences Sequence Analysis Research Article Protein Binding Proteases Livestock Bioinformatics Science Biology Research and Analysis Methods Host Specificity General Biochemistry Genetics and Molecular Biology Gene product 03 medical and health sciences Viral Proteins Species Specificity Electrostatics Antigens Neoplasm medicine Animals Humans Protein Interaction Domains and Motifs Amino Acid Sequence Ubiquitins 030304 developmental biology Innate immune system Protease Sheep Ubiquitin Interferon-stimulated gene Shrews Organisms Biology and Life Sciences Ganjam virus biology.organism_classification ISG15 HEK293 Cells Amniotes Sequence Alignment Peptide Hydrolases |
| Zdroj: | PLOS ONE PLoS ONE PLoS ONE, Vol 14, Iss 12, p e0226415 (2019) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0226415 |
| Popis: | Tick-borne nairoviruses (order Bunyavirales) encode an ovarian tumor domain protease (OTU) that suppresses the innate immune response by reversing the post-translational modification of proteins by ubiquitin (Ub) and interferon-stimulated gene product 15 (ISG15). Ub is highly conserved across eukaryotes, whereas ISG15 is only present in vertebrates and shows substantial sequence diversity. Prior attempts to address the effect of ISG15 diversity on viral protein-ISG15 interactions have focused on only a single species' ISG15 or a limited selection of nairovirus OTUs. To gain a more complete perspective of OTU-ISG15 interactions, we biochemically assessed the relative activities of 14 diverse nairovirus OTUs for 12 species' ISG15 and found that ISG15 activity is predominantly restricted to particular nairovirus lineages reflecting, in general, known virus-host associations. To uncover the underlying molecular factors driving OTUs affinity for ISG15, X-ray crystal structures of Kupe virus and Ganjam virus OTUs bound to sheep ISG15 were solved and compared to complexes of Crimean-Congo hemorrhagic fever virus and Erve virus OTUs bound to human and mouse ISG15, respectively. Through mutational and structural analysis seven residues in ISG15 were identified that predominantly influence ISG15 species specificity among nairovirus OTUs. Additionally, OTU residues were identified that influence ISG15 preference, suggesting the potential for viral OTUs to adapt to different host ISG15s. These findings provide a foundation to further develop research methods to trace nairovirus-host relationships and delineate the full impact of ISG15 diversity on nairovirus infection. |
| Databáze: | OpenAIRE |
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