Codon Usage in HIV-1
Synonymous codons are different codon sequences that encode for the same amino acid. Synonymous codons are not used randomly, and most species have either a bias toward AU- or GC-rich codons in their genomes. Selected groups of viruses, including HIV-1, have evolved to use AU-rich codons for protein synthesis. Interestingly, the natural hosts of these viruses rely on a completely different subset of codons (GC-rich codons) and transfer RNAs (tRNAs) for the incorporation of the same amino acids into the nascent synthesised peptide chains. It is generally assumed that maximum expression of a foreign gene can be achieved by matching the codon bias between the foreign gene and the target host (codon optimisation). As the codon utilised by these viruses are distinct from their natural host cells, the reliance of rare AU-rich codon tRNAs in the host cell would limit the rate of viral protein synthesis and subsequently restricts the levels of infectious virion particle production. The evolution conservation of these bias codons in viral genomes however argues that such ‘limitations’ are well tolerated by the viruses. Furthermore, The objectives of this project is to define the precise mechanism of codon bias in supporting viral replication remains unknown.
Funding Support: National Health and Medical Research Council (NHMRC) and Pfizer Foundation