Modulation of apoptosis and immune signaling pathways by the Hantaan virus nucleocapsid protein.
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-kappaB) 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-kappaB 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.
Graduate Program in Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Steven J
SJ
Ontiveros
Qianjun
Q
Li
Colleen B
CB
Jonsson
D000818:Animals; D017209:Apoptosis; D036022:Capsid Proteins / Q000276:immunology / Q000502:physiology*; D061945:Caspase Inhibitors; D002522:Chlorocebus aethiops; D018063:Hantaan virus / Q000276:immunology / Q000472:pathogenicity*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014709:Vero Cells; D014758:Viral Core Proteins / Q000276:immunology / Q000502:physiology*; D037521:Virulence Factors / Q000276:immunology / Q000502:physiology*
D036022:Capsid Proteins; D061945:Caspase Inhibitors; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; D037521:Virulence Factors; C111782:nucleocapsid protein, Hantaan virus