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Journal of Virology, January 2001, p. 181-191, Vol. 75, No. 1
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.1.181-191.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The Human Immunodeficiency Virus Type 1 gag Gene Encodes an Internal Ribosome Entry Site

Christopher B. Buck,1 Xuefei Shen,2 Michael A. Egan,2 Theodore C. Pierson,3 Christopher M. Walker,4 and Robert F. Siliciano3,*

Program in Cellular and Molecular Medicine,1 Program in Biochemistry, Cellular and Molecular Biology,2 and Graduate Program in Immunology,3 Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, and Department of Virology, Chiron Corporation, Emeryville, California 946084

Received 8 May 2000/Accepted 5 October 2000

Several retroviruses have recently been shown to promote translation of their gag gene products by internal ribosome entry. In this report, we show that mRNAs containing the human immunodeficiency virus type 1 (HIV-1) gag open reading frame (ORF) exhibit internal ribosome entry site (IRES) activity that can promote translational initiation of Pr55gag. Remarkably, this IRES activity is driven by sequences within the gag ORF itself and is not dependent on the native gag 5'-untranslated region (UTR). This cap-independent mechanism for Pr55gag translation may help explain the high levels of translation of this protein in the face of major RNA structural barriers to scanning ribosomes found in the gag 5' UTR. The gag IRES activity described here also drives translation of a novel 40-kDa Gag isoform through translational initiation at an internal AUG codon found near the amino terminus of the Pr55gag capsid domain. Our findings suggest that this low-abundance Gag isoform may be important for wild-type replication of HIV-1 in cultured cells. The activities of the HIV-1 gag IRES may be an important feature of the HIV-1 life cycle and could serve as a novel target for antiretroviral therapeutic strategies.

* Corresponding author. Mailing address: Graduate Program in Immunology, Johns Hopkins University School of Medicine, 720 Rutland Ave., Ross 1059, Baltimore, MD 21205. Phone: (410) 955-2958. Fax: (410) 955-0964. E-mail: rsilicia{at}welch.jhu.edu.

Journal of Virology, January 2001, p. 181-191, Vol. 75, No. 1
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.1.181-191.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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