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Modulation of apoptosis and immune signaling pathways by the Hantaan virus nucleocapsid protein |
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| Authors: | Steven J. Ontiveros Colleen B. Jonsson |
| Affiliation: | a Graduate Program in Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA b Department of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, USA c Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, AL 35205, USA d Department of Microbiology and Immunology, University of Louisville, KY 40402, USA e Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, KY 40402, USA |
| Abstract: | Herein, we show a direct relationship between the Hantaan virus (HTNV) nucleocapsid (N) protein and the modulation of apoptosis. We observed an increase in caspase-7 and -8, but not -9 in cells expressing HTNV N protein mutants lacking amino acids 270-330. Similar results were observed for the New World hantavirus, Andes virus. Nuclear factor kappa B (NF-κB) was sequestered in the cytoplasm after tumor necrosis factor receptor (TNFR) stimulation in cells expressing HTNV N protein. Further, TNFR stimulated cells expressing HTNV N protein inhibited caspase activation. In contrast, cells expressing N protein truncations lacking the region from amino acids 270-330 were unable to inhibit nuclear import of NF-κB and the mutants also triggered caspase activity. These results suggest that the HTNV circumvents host antiviral signaling and apoptotic response mediated by the TNFR pathway through host interactions with the N protein. |
| Keywords: | Hantavirus Nucleocapsid protein Hantaan virus Apoptosis |
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