Journal
VIROLOGY
Volume 401, Issue 2, Pages 165-178Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2010.02.018
Keywords
Hantavirus; Nucleocapsid protein; Hantaan virus; Apoptosis
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Funding
- Southern Research Institute
- National Institutes of Health [5 R21 AI06699-0]
- Department of Defense [W81XWH-04-C-0055]
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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-kappa B) 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-kappa B 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. (C) 2010 Elsevier Inc. All rights reserved.
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