Death effector domain-containing herpesvirus and poxvirus proteins inhibit both Fas- and TNFR1-induced apoptosis.
To identify novel antiapoptotic proteins encoded by DNA viruses, we searched viral genomes for proteins that might interfere with Fas and TNFR1 apoptotic signaling pathways. We report here that equine herpesvirus type 2 E8 protein and molluscum contagiosum virus MC159 protein both show sequence similarity to the death effector domains (DEDs) of the Fas/TNFR1 signaling components FADD and caspase-8. Yeast two-hybrid analysis revealed that E8 protein interacted with the caspase-8 prodomain whereas MC159 protein interacted with FADD. Furthermore, expression of either E8 protein or MC159 protein protected cells from Fas- and TNFR1-induced apoptosis indicating that certain herpesviruses and poxviruses use DED-mediated interactions to interfere with apoptotic signaling pathways. These findings identify a novel control point exploited by viruses to regulate Fas- and TNFR1-mediated apoptosis.
Bertin
J
J
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Armstrong
R C
RC
Ottilie
S
S
Martin
D A
DA
Wang
Y
Y
Banks
S
S
Wang
G H
GH
Senkevich
T G
TG
Alnemri
E S
ES
Moss
B
B
Lenardo
M J
MJ
Tomaselli
K J
KJ
Cohen
J I
JI
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004267:DNA Viruses; D053200:Fas-Associated Death Domain Protein; D006564:Herpesviridae; D008954:Models, Biological; D008969:Molecular Sequence Data; D008977:Molluscum contagiosum virus; D011485:Protein Binding; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014764:Viral Proteins / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D002352:Carrier Proteins; D053200:Fas-Associated Death Domain Protein; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014764:Viral Proteins; D019014:fas Receptor; D003546:Cysteine Endopeptidases