An AUG codon upstream of rev and env open reading frames ensures optimal translation of the simian immunodeficiency virus Env protein

► The SIV mRNAs encoding Rev and Env protein have an upstream AUG codon. ► This upstream uAUG4 down-regulates Rev protein expression. ► By down-regulating Rev translation, uAUG4 up-regulates Env translation. ► uAUG4 “Kozak strength” and overlap with the Rev ORF ensure optimal Env translation. ► uORF4 is an important regulatory motif for optimal viral replication fitness.