This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guo, X.
Right arrow Articles by Gao, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guo, X.
Right arrow Articles by Gao, G.

 Previous Article  |  Next Article 

Journal of Virology, December 2004, p. 12781-12787, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.12781-12787.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Zinc Finger Antiviral Protein Directly Binds to Specific Viral mRNAs through the CCCH Zinc Finger Motifs

Xuemin Guo,1,2 John-William N. Carroll,3 Margaret R. MacDonald,3 Stephen P. Goff,4 and Guangxia Gao1*

Institute of Microbiology,1 Graduate School, Chinese Academy of Sciences, Beijing, China,2 Laboratory of Virology and Infectious Diseases, The Rockefeller University,3 Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, New York4

Received 20 May 2004/ Accepted 21 July 2004

The zinc finger antiviral protein (ZAP) is a recently isolated host antiviral factor. It specifically inhibits the replication of Moloney murine leukemia virus (MLV) and Sindbis virus (SIN) by preventing the accumulation of viral RNA in the cytoplasm. For this report, we mapped the viral sequences that are sensitive to ZAP inhibition. The viral sequences were cloned into a luciferase reporter and analyzed for the ability to mediate ZAP-dependent destabilization of the reporter. The sensitive sequence in MLV was mapped to the 3' long terminal repeat; the sensitive sequences in SIN were mapped to multiple fragments. The fragment of SIN that displayed the highest destabilizing activity was further analyzed by deletion mutagenesis for the minimal sequence that retained the activity. This led to the identification of a fragment of 653 nucleotides. Any further deletion of this fragment resulted in significantly lower activity. We provide evidence that ZAP directly binds to the active but not the inactive fragments. The CCCH zinc finger motifs of ZAP play important roles in RNA binding and antiviral activity. Disruption of the second and fourth zinc fingers abolished ZAP's activity, whereas disruption of the first and third fingers just slightly lowered its activity.

* Corresponding author. Mailing address: Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China. Phone: (86)-10-62653563. Fax: (86)-10-62653562. E-mail: gaogx{at}sun.im.ac.cn.

Journal of Virology, December 2004, p. 12781-12787, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.12781-12787.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Teotia, S., Lamb, R. S. (2009). The Paralogous Genes RADICAL-INDUCED CELL DEATH1 and SIMILAR TO RCD ONE1 Have Partially Redundant Functions during Arabidopsis Development. Plant Physiol. 151: 180-198 [Abstract] [Full Text]  
  • Aguilar, P. V., Adams, A. P., Wang, E., Kang, W., Carrara, A.-S., Anishchenko, M., Frolov, I., Weaver, S. C. (2008). Structural and Nonstructural Protein Genome Regions of Eastern Equine Encephalitis Virus Are Determinants of Interferon Sensitivity and Murine Virulence. J. Virol. 82: 4920-4930 [Abstract] [Full Text]  
  • Chen, G., Guo, X., Lv, F., Xu, Y., Gao, G. (2008). p72 DEAD box RNA helicase is required for optimal function of the zinc-finger antiviral protein. Proc. Natl. Acad. Sci. USA 105: 4352-4357 [Abstract] [Full Text]  
  • MacDonald, M. R., Machlin, E. S., Albin, O. R., Levy, D. E. (2007). The Zinc Finger Antiviral Protein Acts Synergistically with an Interferon-Induced Factor for Maximal Activity against Alphaviruses. J. Virol. 81: 13509-13518 [Abstract] [Full Text]  
  • Muller, S., Moller, P., Bick, M. J., Wurr, S., Becker, S., Gunther, S., Kummerer, B. M. (2007). Inhibition of Filovirus Replication by the Zinc Finger Antiviral Protein. J. Virol. 81: 2391-2400 [Abstract] [Full Text]  
  • Guo, X., Ma, J., Sun, J., Gao, G. (2007). The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA. Proc. Natl. Acad. Sci. USA 104: 151-156 [Abstract] [Full Text]  
  • Kozak, S. L., Marin, M., Rose, K. M., Bystrom, C., Kabat, D. (2006). The Anti-HIV-1 Editing Enzyme APOBEC3G Binds HIV-1 RNA and Messenger RNAs That Shuttle between Polysomes and Stress Granules. J. Biol. Chem. 281: 29105-29119 [Abstract] [Full Text]  
  • Bishop, K. N., Mortuza, G. B., Howell, S., Yap, M. W., Stoye, J. P., Taylor, I. A. (2006). Characterization of an amino-terminal dimerization domain from retroviral restriction factor fv1.. J. Virol. 80: 8225-8235 [Abstract] [Full Text]  
  • Triantis, V., Trancikova, D. E., Looman, M. W. G., Hartgers, F. C., Janssen, R. A. J., Adema, G. J. (2006). Identification and Characterization of DC-SCRIPT, a Novel Dendritic Cell-Expressed Member of the Zinc Finger Family of Transcriptional Regulators. J. Immunol. 176: 1081-1089 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»