A point mutation, E95D, in the mumps virus V protein disengages STAT3 targeting from STAT1 targeting.
Mumps virus, like other paramyxoviruses in the Rubulavirus genus, encodes a V protein that can assemble a ubiquitin ligase complex from cellular components, leading to the destruction of cellular signal transducer and activator of transcription (STAT) proteins. While many V proteins target the interferon-activated STAT1 or STAT2 protein, mumps virus V protein is unique in its ability to also target STAT3 for ubiquitin modification and proteasome-mediated degradation. Here we report that a single amino acid substitution in the mumps virus V protein, E95D, results in defective STAT3 targeting while maintaining the ability to target STAT1. Results indicate that the E95D mutation disrupts the ability of the V protein to associate with STAT3. A recombinant mumps virus carrying the E95D mutation in its P and V proteins replicates normally in cultured cells but fails to induce targeting of STAT3. Infection with the recombinant virus results in the differential regulation of a number of cellular genes compared to wild-type mumps virus and increases cell death in infected cells, producing a large-plaque phenotype.
Puri
Mamta
M
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500, USA.
Lemon
Ken
K
Duprex
W Paul
WP
Rima
Bertus K
BK
Horvath
Curt M
CM
D019943:Amino Acid Substitution; D000818:Animals; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D009107:Mumps / Q000821:virology; D009109:Mumps virus / Q000235:genetics* / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D020411:Oligonucleotide Array Sequence Analysis; D017354:Point Mutation; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014764:Viral Proteins