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

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Abstract
Several retroviruses have recently been shown to promote translation of theirgaggene products by internal ribosome entry. In this report, we show that mRNAs containing the human immunodeficiency virus type 1 (HIV-1)gagopen 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 thegagORF itself and is not dependent on the nativegag5′-untranslated region (UTR). This cap-independent mechanism for Pr55gagtranslation may help explain the high levels of translation of this protein in the face of major RNA structural barriers to scanning ribosomes found in thegag5′ UTR. ThegagIRES 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 Pr55gagcapsid 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-1gagIRES may be an important feature of the HIV-1 life cycle and could serve as a novel target for antiretroviral therapeutic strategies.

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