Upstream AUG codons in the simian immunodeficiency virus SIVmac239 genome regulate Rev and Env protein translation

The mRNAs encoding the Rev and Env proteins of simian immunodeficiency virus (SIV) are unique because upstream translation start codons are present that may modulate the expression of these viral proteins. This is true for the regular mRNAs, but we also report novel mRNA splicing variants that encode up to five upstream AUG (uAUG) codons. Their influence on Rev and Env translation was measured by mutational inactivation in reporter constructs and in the SIVmac239 strain. An intricate regulatory mechanism was disclosed that allows the virus to express a balanced amount of these two proteins. This insight also allows the design of vector constructs that efficiently express these proteins.