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Journal of Virology, April 2005, p. 4308-4315, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4308-4315.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Role of a Cytotoxic-T-Lymphocyte Epitope-Defined, Alternative gag Open Reading Frame in the Pathogenesis of a Murine Retrovirus-Induced Immunodeficiency Syndrome

Arti Gaur* and William R. Green

Department of Microbiology and Immunology and the Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire

Received 10 August 2004/ Accepted 3 November 2004

LP-BM5 murine leukemia virus-infected C57BL/6 mice develop profound immunodeficiency and B-cell lymphomas. The LP-BM5 complex contains a mixture of defective (BM5def) and replication-competent helper viruses among which BM5def is the primary causative agent of disease. The BM5def primary open reading frame (ORF1) encodes the single gag precursor protein (Pr60gag). Our lab has recently demonstrated that a novel immunodominant cytotoxic-T-lymphocyte (CTL) epitope (SYNTGRFPPL) is expressed from a +1-nucleotide translational open reading frame of BM5def during the course of normal retrovirus expression. The SYNTGRFPPL CTL epitope may be generated from either of two initiation methionines present, ORF2a or ORF2b, located downstream of the ORF1 initiation site. This study investigates the role(s) of the alternative ORF2-derived gag protein(s) of BM5def in viral pathogenesis. We have examined the disease-inducing capabilities of mutant viruses in which the translational potential of either the initiating ORF2a or ORF2b AUG has been disrupted. Although these mutated viruses are capable of wild-type ORF1 expression, they are unable to induce disease. Our data strongly suggest the existence of a novel ORF2 product(s) that is required for LP-BM5-induced pathogenesis and have potentially broad implications for other retroviral diseases.

* Corresponding author. Mailing address: Dartmouth Medical School, Department of Microbiology and Immunology, 626W Borwell, One Medical Center Dr., Lebanon, NH 03756. Phone: (603) 650-5056. Fax: (603) 650-6223. E-mail: Arti.Gaur{at}dartmouth.edu.

Journal of Virology, April 2005, p. 4308-4315, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4308-4315.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yewdell, J. W., Hickman, H. D. (2007). New lane in the information highway: alternative reading frame peptides elicit T cells with potent antiretrovirus activity. JEM 204: 2501-2504 [Abstract] [Full Text]  
  • Ho, O., Green, W. R. (2006). Alternative Translational Products and Cryptic T Cell Epitopes: Expecting the Unexpected. J. Immunol. 177: 8283-8289 [Abstract] [Full Text]  


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