CODON USAGE LIMITATION IN THE EXPRESSION OF HIV-1 ENVELOPE GLYCOPROTEIN

Background: The expression of both the env and gag gene products of hu man immunodeficiency virus type 1 (HIV-I) is known to be limited by ci s elements in the viral RNA that impede egress from the nucleus and re duce the efficiency of translation, Identifying these elements has pro ven difficult, as they appear to be disseminated throughout the viral genome. Results: Here, we report that selective codon usage appears to account for a substantial fraction of the inefficiency of viral prote in synthesis, independent of any effect on improved nuclear export, Th e codon usage effect is not specific to transcripts of HIV-1 origin. R e-engineering the coding sequence of a model protein (Thy-1) with the most prevalent HIV-1 codons significantly impairs Thy-1 expression, wh ereas altering the coding sequence of the jellyfish green fluorescent protein gene to conform to the favored codons of highly expressed huma n proteins results in a substantial increase in expression efficiency, Conclusions: Codon-usage effects are a major impediment to the effici ent expression of HIV-I genes, Although mammalian genes do not show as profound a bias as do Escherichia coli genes, other proteins that are poorly expressed in mammalian cells can benefit from codon re-enginee ring.