Domain within the C protein of human parainfluenza virus type 3 that regulates interferon signaling.
Human parainfluenza virus type 3 (HPIV3), one of the paramyxoviruses, uses its accessory C protein as an antagonist against interferon (IFN)-mediated host innate immunity. We have previously shown that the C protein significantly decreased the IFN-induced phosphorylation of signal transducer and activator of transcription (Stat) 1 and the formation of gamma IFN activation factor (GAF) complex, thus abrogating the antiviral activity of the IFNs against vesicular stomatitis virus (VSV) replication. Here, by mutational analyses we demonstrated that the N-terminal truncation of the C protein (CNdelta25 and CNdelta50) substantially (approximately 50%) recovers the IFN-induced responses, suggesting the critical role of the N-terminal region of the C protein in IFN signaling. Furthermore, our results indicate that the charged amino acid residues within the N-terminal region of the C protein regulate the antagonistic effect of the C protein on IFN signaling.
Virology Section, Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Hongxia
H
Mao
Santanu
S
Chattopadhyay
Amiya K
AK
Banerjee
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000378:metabolism* / Q000494:pharmacology; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010224:Parainfluenza Virus 3, Human / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017434:Protein Structure, Tertiary; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D053634:TYK2 Kinase / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic / Q000187:drug effects; D018116:Vesiculovirus / Q000187:drug effects / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism*
D000998:Antiviral Agents; D050505:Mutant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014764:Viral Proteins; D007372:Interferons; D053634:TYK2 Kinase; C070139:TYK2 protein, human