Inhibition of TNF-alpha-induced activation of NF-kappaB by hantavirus nucleocapsid proteins.
Hantaviruses cause two human diseases thought to be immune-mediated: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). We recently reported that the nucleocapsid (N) protein of HFRS-causing Hantaan virus (HTNV) inhibits tumor necrosis factor-alpha (TNF-alpha) activation of nuclear factor-kappaB (NF-kappaB). Here we measured the ability of other hantaviral N proteins to similarly interfere with the inflammatory process of TNF-alpha. We found that like HTNV N, the N proteins of HFRS-causing Seoul and Dobrava viruses inhibited TNF-alpha activation of NF-kappaB and translocation of the NF-kappaB p65 subunit, but did not interfere with degradation of inhibitor of NF-kappaB (IkappaB). In contrast, the HFRS-causing Puumala virus and the HPS-causing Andes and Sin Nombre viruses did not prevent TNF-alpha activation of NF-kappaB or nuclear translocation of p65. These studies provide evidence that hantaviruses differ in their abilities to interfere with host innate immune responses.
Taylor
Shannon L
SL
Science & Technology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702, USA.
Krempel
Ryan L
RL
Schmaljohn
Connie S
CS
D001208:Asia / Q000453:epidemiology; D002460:Cell Line; D005060:Europe / Q000453:epidemiology; D017930:Genes, Reporter; D016679:Genome, Viral; D005843:Geography; D049452:Green Fluorescent Proteins / Q000235:genetics; D006476:Orthohantavirus / Q000235:genetics / Q000378:metabolism*; D018804:Hantavirus Pulmonary Syndrome / Q000453:epidemiology / Q000821:virology; D006480:Hemorrhagic Fever with Renal Syndrome / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D007668:Kidney / Q000196:embryology / Q000821:virology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D019590:Nucleocapsid Proteins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
D016328:NF-kappa B; D019590:Nucleocapsid Proteins; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins