TY - JOUR
T1 - Homo-oligomerization facilitates the interferon-antagonist activity of the ebolavirus VP35 protein
AU - Reid, St Patrick
AU - Cárdenas, Washington B.
AU - Basler, Christopher F.
N1 - Funding Information:
This work was supported by NIH grants to C.F.B. C.F.B. is an Ellison Medical Foundation New Scholar in Global Infectious Diseases. S.P.R. is a predoctoral trainee and was supported in part by a United States Public Health Service Institutional Research Training Award (AI 07647). W.B.C. is the recipient of a post-doctoral fellowship provided by the Northeast Biodefense Center, a Regional Center of Excellence (RCE) for Biodefense and Emerging Infectious Diseases Research. We thank Dr. Patricia Cortes and Pablo De Ioannes, Immunobiology Center, Mount Sinai School of Medicine, for assistance with gel filtration. We also thank Dr. Ganes Sen, Cleveland Clinic and Dr. James Stevens and Dr. Ian Wilson, the Scripps Research Institute and Adolfo García-Sastre and Luis Martinez-Sobrido, Mount Sinai School of Medicine, for providing reagents. Mauricio Sanchez provided excellent technical support to this work.
PY - 2005/10/25
Y1 - 2005/10/25
N2 - We have identified a putative coiled-coil motif within the amino-terminal half of the ebolavirus VP35 protein. Cross-linking studies demonstrated the ability of VP35 to form trimers, consistent with the presence of a functional coiled-coil motif. VP35 mutants lacking the coiled-coil motif or possessing a mutation designed to disrupt coiled-coil function were defective in oligomerization, as deduced by co-immunoprecipitation studies. VP35 inhibits signaling that activates interferon regulatory factor 3 (IRF-3) and inhibits (IFN)-α/β production. Experiments comparing the ability of VP35 mutants to block IFN responses demonstrated that the VP35 amino-terminus, which retains the putative coiled-coil motif, was unable to inhibit IFN responses, whereas the VP35 carboxy-terminus weakly inhibited the activation of IFN responses. IFN-antagonist function was restored when a heterologous trimerization motif was fused to the carboxy-terminal half of VP35, suggesting that an oligomerization function at the amino-terminus facilitates an "IFN-antagonist" function exerted by the carboxy-terminal half of VP35.
AB - We have identified a putative coiled-coil motif within the amino-terminal half of the ebolavirus VP35 protein. Cross-linking studies demonstrated the ability of VP35 to form trimers, consistent with the presence of a functional coiled-coil motif. VP35 mutants lacking the coiled-coil motif or possessing a mutation designed to disrupt coiled-coil function were defective in oligomerization, as deduced by co-immunoprecipitation studies. VP35 inhibits signaling that activates interferon regulatory factor 3 (IRF-3) and inhibits (IFN)-α/β production. Experiments comparing the ability of VP35 mutants to block IFN responses demonstrated that the VP35 amino-terminus, which retains the putative coiled-coil motif, was unable to inhibit IFN responses, whereas the VP35 carboxy-terminus weakly inhibited the activation of IFN responses. IFN-antagonist function was restored when a heterologous trimerization motif was fused to the carboxy-terminal half of VP35, suggesting that an oligomerization function at the amino-terminus facilitates an "IFN-antagonist" function exerted by the carboxy-terminal half of VP35.
KW - Ebolavirus VP35 protein
KW - Homo-oligomerization
KW - Interferon
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U2 - 10.1016/j.virol.2005.06.044
DO - 10.1016/j.virol.2005.06.044
M3 - Article
C2 - 16095644
AN - SCOPUS:26244437083
SN - 0042-6822
VL - 341
SP - 179
EP - 189
JO - Virology
JF - Virology
IS - 2
ER -