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Journal of Virology, November 2007, p. 12337-12347, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.01286-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Mutational Analysis of the N-Terminal Domain of Moloney Murine Leukemia Virus Capsid Protein{triangledown}

Marcy R. Auerbach,{dagger} Kristy R. Brown, and Ila R. Singh*

Department of Pathology, Columbia University Medical Center, 630 West 168th Street, New York, New York 10032

Received 13 June 2007/ Accepted 30 August 2007

Retroviral capsid (CA) proteins contain a structurally conserved N-terminal domain (NTD) consisting of a ß-hairpin and six to seven {alpha}-helices. To examine the role of this domain in Moloney murine leukemia virus (MoMLV) replication, we analyzed 18 insertional mutations in this region. All mutants were noninfectious. Based on the results of this analysis and our previous studies on additional mutations in this domain, we were able to divide the NTD of MoMLV CA into three functional regions. The first functional region included the region near the N terminus that forms the ß-hairpin and was shown to control normal maturation of virions. The second region included the helix 4/5 loop and was essential for the formation of spherical cores. The third region encompassed most of the NTD except for the above loop. Mutants of this region assembled imperfect cores, as seen by detailed electron microscopy analyses, yet the resulting particles were efficiently released from cells. The mutants were defective at a stage immediately following entry of the core into cells. Despite possessing functional reverse transcriptase machinery, these mutant virions did not initiate reverse transcription in cells. This block could be due to structural defects in the assembling core or failure of an essential host protein to interact with the mutant CA protein, both of which may prevent correct disassembly upon entry of the virus into cells. Future studies are needed to understand the mechanism of these blocks and to target these regions pharmacologically to inhibit retroviral infection at additional stages.

* 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

{triangledown} Published ahead of print on 12 September 2007.

{dagger} Present address: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037.

Journal of Virology, November 2007, p. 12337-12347, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.01286-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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