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Journal of Virology, October 2007, p. 10718-10728, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.01061-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Overlapping Roles of the Rous Sarcoma Virus Gag p10 Domain in Nuclear Export and Virion Core Morphology{triangledown}

Lisa Z. Scheifele,1,{dagger} Scott P. Kenney,2 Tina M. Cairns,2,¶ Rebecca C. Craven,2 and Leslie J. Parent1,2*

Departments of Medicine,1 Microbiology and Immunology, the Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 170332

Received 16 May 2007/ Accepted 10 July 2007

Nucleocytoplasmic shuttling of the Rous sarcoma virus (RSV) Gag polyprotein is an integral step in virus particle assembly. A nuclear export signal (NES) was previously identified within the p10 domain of RSV Gag. Gag mutants containing deletions of the p10 NES or mutations of critical hydrophobic residues at positions 219, 222, 225, or 229 become trapped within the nucleus and exhibit defects in the efficiency of virus particle release. To investigate other potential roles for Gag nuclear trafficking in RSV replication, we created viruses bearing NES mutant Gag proteins. Viruses carrying p10 mutations produced low levels of particles, as anticipated, and those particles that were released were noninfectious. The p10 mutant viruses contained approximately normal amounts of Gag, Gag-Pol, and Env proteins and genomic viral RNA (vRNA), but several major structural defects were found. Thin-section transmission electron microscopy revealed that the mature particles appeared misshapen, while the viral cores were cylindrical, horseshoe-shaped, or fragmented, with some particles containing multiple small, electron-dense aggregates. Immature virus-like particles produced by the expression of Gag proteins bearing p10 mutations were also aberrant, with both spherical and tubular filamentous particles produced. Interestingly, the secondary structure of the encapsidated vRNA was altered; although dimeric vRNA was predominant, there was an additional high-molecular-weight fraction. Together, these results indicate that the p10 NES domain of Gag is critical for virus replication and that it plays overlapping roles required for the nuclear shuttling of Gag and for the maintenance of proper virion core morphology.

* Corresponding author. Mailing address: Department of Medicine, the Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033. Phone: (717) 531-3997. Fax: (717) 531-4633. E-mail: lparent{at}psu.edu

{triangledown} Published ahead of print on 18 July 2007.

{dagger} Present address: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 320 Broadway Research Building, 733 North Broadway, Baltimore, MD 21205.

Present address: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104.

Journal of Virology, October 2007, p. 10718-10728, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.01061-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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  • Kenney, S. P., Lochmann, T. L., Schmid, C. L., Parent, L. J. (2008). Intermolecular Interactions between Retroviral Gag Proteins in the Nucleus. J. Virol. 82: 683-691 [Abstract] [Full Text]  


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