The ebolavirus VP24 interferon antagonist: know your enemy.
Suppression during the early phases of the immune system often correlates directly with a fatal outcome for the host. The ebolaviruses, some of the most lethal viruses known, appear to cripple initial stages of the host defense network via multiple distinct paths. Two of the eight viral proteins are critical for immunosuppression. One of these proteins is VP35, which binds double-stranded RNA and antagonizes several antiviral signaling pathways. The other protein is VP24, which binds transporter molecules to prevent STAT1 translocation. A more recent discovery is that VP24 also binds STAT1 directly, suggesting that VP24 may operate in at least two separate branches of the interferon pathway. New crystal structures of VP24 derived from pathogenic and nonpathogenic ebolaviruses reveal its novel, pyramidal fold, upon which can be mapped sites required for virulence and for STAT1 binding. These structures of VP24, and new information about its direct binding to STAT1, provide avenues by which we may explore its many roles in the viral life cycle, and reasons for differences in pathogenesis among the ebolaviruses.
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
Adrianna P P
AP
Zhang
Dafna M
DM
Abelson
Zachary A
ZA
Bornholdt
Tong
T
Liu
Virgil L
VL
Woods
Erica Ollmann
EO
Saphire
D018360:Crystallography, X-Ray; D029043:Ebolavirus / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D057131:Immune Evasion; D007108:Immune Tolerance; D007372:Interferons / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D037521:Virulence Factors / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C446938:VP24 protein, Ebola virus; D014764:Viral Proteins; D037521:Virulence Factors; D007372:Interferons