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Journal of Virology, March 2006, p. 2884-2893, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2884-2893.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A Small Loop in the Capsid Protein of Moloney Murine Leukemia Virus Controls Assembly of Spherical Cores

Marcy R. Auerbach,1,2 Kristy R. Brown,1 Artem Kaplan,1 Denise de Las Nueces,1,{dagger} and Ila R. Singh1*

Department of Pathology, Columbia University Medical Center, 630 West 168th Street, New York, New York 10032,1 Integrated Program in Cellular, Molecular, and Biophysical Studies, Columbia University College of Physicians and Surgeons, New York, New York 100322

Received 4 October 2005/ Accepted 27 December 2005

We report the identification of a novel domain in the Gag protein of Moloney murine leukemia virus (MoLV) that is important for the formation of spherical cores. Analysis of 18 insertional mutations in the N-terminal domain of the capsid protein (CA) identified 3 that were severely defective for viral assembly and release. Transmission electron microscopy of cells producing these mutants showed assembly of Gag proteins in large, flat or dome-shaped patches at the plasma membrane. Spherical cores were not formed, and viral particles were not released. This late assembly/release block was partially rescued by wild-type virus. All three mutations localized to the small loop between {alpha}-helices 4 and 5 of CA, analogous to the cyclophilin A-binding loop of human immunodeficiency virus type 1 CA. In the X-ray structure of the hexameric form of MLV CA, this loop is located at the periphery of the hexamer. The phenotypes of mutations in this loop suggest that formation of a planar lattice of Gag is unhindered by mutations in the loop. However, the lack of progression of these planar structures to spherical ones suggests that mutations in this loop may prevent formation of pentamers or of stable pentamer-hexamer interactions, which are essential for the formation of a closed, spherical core. This region in CA, focused to a few residues of a small loop, may offer a novel therapeutic target for retroviral diseases.

* Corresponding author. Mailing address: Department of Pathology, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032. Phone: (212) 305-4263. Fax: (212) 305-4189. E-mail: is132{at}columbia.edu.

{dagger} Present address: Harvard Medical School, Boston, MA 02115.

Journal of Virology, March 2006, p. 2884-2893, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2884-2893.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Auerbach, M. R., Brown, K. R., Singh, I. R. (2007). Mutational Analysis of the N-Terminal Domain of Moloney Murine Leukemia Virus Capsid Protein. J. Virol. 81: 12337-12347 [Abstract] [Full Text]  


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