Severe acute respiratory syndrome coronavirus protein 6 mediates ubiquitin-dependent proteosomal degradation of N-Myc (and STAT) interactor
- 495 Downloads
Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes eight accessory proteins, the functions of which are not yet fully understood. SARS-CoV protein 6 (P6) is one of the previously studied accessory proteins that have been documented to enhance viral replication and suppress host interferon (IFN) signaling pathways. Through yeast two-hybrid screening, we identified eight potential cellular P6-interacting proteins from a human spleen cDNA library. For further investigation, we targeted the IFN signaling pathway-mediating protein, N-Myc (and STAT) interactor (Nmi). Its interaction with P6 was confirmed within cells. The results showed that P6 can promote the ubiquitin-dependent proteosomal degradation of Nmi. This study revealed a new mechanism of SARS-CoV P6 in limiting the IFN signaling to promote SARS-CoV survival in host cells.
Keywordssevere acute respiratory syndrome coronavirus (SARS-CoV) P6 N-Myc (and STAT) interactor (Nmi) interferon (IFN) signaling pathway ubiquitination proteosomal degradation
Unable to display preview. Download preview PDF.
- Chen CY, Ping YH, Lee HC, Chen KH, Lee YM, Chan YJ, Lien TC, Jap TS, Lin CH, Kao LS, Chen YM. 2007. Open reading frame 8a of the human severe acute respiratory syndrome coronavirus not only promotes viral replication but also induces apoptosis. J Infect Dis, 196: 405–415.CrossRefPubMedGoogle Scholar
- Frieman M, Yount B, Heise M, Kopecky-Bromberg SA, Palese P, Baric RS. 2007. Severe acute respiratory syndrome coronavirus orf6 antagonizes stat1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/golgi membrane. J Virol, 81: 9812–9824.CrossRefPubMedCentralPubMedGoogle Scholar
- Guan Y, Zheng BJ, He YQ, Liu XL, Zhuang ZX, Cheung CL, Luo SW, Li PH, Zhang LJ, Guan YJ, Butt KM, Wong KL, Chan KW, Lim W, Shortridge KF, Yuen KY, Peiris JS, Poon LL. 2003. Isolation and characterization of viruses related to the sars coronavirus from animals in southern china. Science, 302: 276–278.CrossRefPubMedGoogle Scholar
- Haagmans BL, Kuiken T, Martina BE, Fouchier RA, Rimmelz-waan GF, van Amerongen G, van Riel D, de Jong T, Itamura S, Chan KH, Tashiro M, Osterhaus AD. 2004. Pegylated interferon-alpha protects type 1 pneumocytes against sars coronavirus infection in macaques. Nat Med, 10: 290–293.CrossRefPubMedGoogle Scholar
- Lundberg L, Pinkham C, Baer A, Amaya M, Narayanan A, Wagstaff KM, Jans DA, Kehn-Hall K. 2013. Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce venezuelan equine encephalitis virus replication. Antiviral Res, 100: 662–672.CrossRefPubMedGoogle Scholar
- Netland J, Ferraro D, Pewe L, Olivares H, Gallagher T, Perlman S. 2007. Enhancement of murine coronavirus replication by severe acute respiratory syndrome coronavirus protein 6 requires the n-terminal hydrophobic region but not c-terminal sorting motifs. J Virol, 81: 11520–11525.CrossRefPubMedCentralPubMedGoogle Scholar
- Spiegel M, Pichlmair A, Martinez-Sobrido L, Cros J, Garcia-Sastre A, Haller O, Weber F. 2005. Inhibition of beta interferon induction by severe acute respiratory syndrome coronavirus suggests a two-step model for activation of interferon regulatory factor 3. J Virol, 79: 2079–2086.CrossRefPubMedCentralPubMedGoogle Scholar
- Yount B, Roberts RS, Sims AC, Deming D, Frieman MB, Sparks J, Denison MR, Davis N, Baric RS. 2005. Severe acute respiratory syndrome coronavirus group-specific open reading frames encode nonessential functions for replication in cell cultures and mice. J Virol, 79: 14909–14922.CrossRefPubMedCentralPubMedGoogle Scholar
- Zhou H, Ferraro D, Zhao J, Hussain S, Shao J, Trujillo J, Netland J, Gallagher T, Perlman S. 2010. The n-terminal region of severe acute respiratory syndrome coronavirus protein 6 induces membrane rearrangement and enhances virus replication. J Virol, 84: 3542–3551.CrossRefPubMedCentralPubMedGoogle Scholar