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Journal of Virology, July 2008, p. 6972-6983, Vol. 82, No. 14
0022-538X/08/$08.00+0     doi:10.1128/JVI.01283-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Five-Amino-Acid Deletion of the Eastern Equine Encephalitis Virus Capsid Protein Attenuates Replication in Mammalian Systems but Not in Mosquito Cells{triangledown}

Patricia V. Aguilar,1* Lawrence W. Leung,1 Eryu Wang,2,3 Scott C. Weaver,2,3 and Christopher F. Basler1*

Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029,1 Center for Biodefense and Emerging Infectious Diseases,2 Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-06093

Received 12 June 2007/ Accepted 7 May 2008

Eastern equine encephalitis virus (EEEV) is a human and veterinary pathogen that causes sporadic cases of fatal neurological disease. We previously demonstrated that the capsid protein of EEEV is a potent inhibitor of host cell gene expression and that this function maps to the amino terminus of the protein. We now identify amino acids 55 to 75, within the N terminus of the capsid, as critical for the inhibition of host cell gene expression. An analysis of stable EEEV replicons expressing mutant capsid proteins corroborated these mapping data. When deletions of 5 to 20 amino acids within this region of the capsid were introduced into infectious EEEV, the mutants exhibited delayed replication in Vero cells. However, the replication of the 5-amino-acid deletion mutant in C710 mosquito cells was not affected, suggesting that virus replication and assembly were affected in a cell-specific manner. Both 5- and 20-amino-acid deletion mutant viruses exhibited increased sensitivity to interferon (IFN) in cell culture and impaired replication and complete attenuation in mice. In summary, we have identified a region within the capsid protein of EEEV that contributes to the inhibition of host gene expression and to the protection of EEEV from the antiviral effects of IFNs. This region is also critical for EEEV pathogenesis.

* Corresponding author. Mailing address: Department of Microbiology, Box 1124, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029. Phone for Patricia V. Aguilar: (212) 241-4386. Fax: (212) 534-1684. E-mail: patricia.aguilar{at}mssm.edu. Phone for Christopher F. Basler: (212) 241-4847. Fax: (212) 534-1684. E-mail: chris.basler{at}mssm.edu

{triangledown} Published ahead of print on 14 May 2008.

Journal of Virology, July 2008, p. 6972-6983, Vol. 82, No. 14
0022-538X/08/$08.00+0     doi:10.1128/JVI.01283-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Simmons, J. D., White, L. J., Morrison, T. E., Montgomery, S. A., Whitmore, A. C., Johnston, R. E., Heise, M. T. (2009). Venezuelan Equine Encephalitis Virus Disrupts STAT1 Signaling by Distinct Mechanisms Independent of Host Shutoff. J. Virol. 83: 10571-10581 [Abstract] [Full Text]  
  • Gardner, C. L., Burke, C. W., Tesfay, M. Z., Glass, P. J., Klimstra, W. B., Ryman, K. D. (2008). Eastern and Venezuelan Equine Encephalitis Viruses Differ in Their Ability To Infect Dendritic Cells and Macrophages: Impact of Altered Cell Tropism on Pathogenesis. J. Virol. 82: 10634-10646 [Abstract] [Full Text]  


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