Young C. Shina,1, Georg F. Bischofa,b,1, William A. Lauera, and Ronald C. Desrosiersa,2
aDepartment of Pathology, Miller School of Medicine, University of Miami, Miami, FL 33136;
bInstitute of Clinical and Molecular Virology, Friedrich-Alexander-Universitat Erlangen-Nurnberg, 91054 Erlangen, Germany
Abstract
The glycoproteins of herpesviruses and of HIV/SIV are made late in the replication cycle and are derived from transcripts that use an unusual codon usage that is quite different from that of the host cell. Here we show that the actions of natural transinducers from these two different families of persistent viruses (Rev of SIV and ORF57 of the rhesus monkey rhadinovirus) are dependent on the nature of the skewed codon usage. In fact, the transinducibility of expression of these glycoproteins by Rev and by ORF57 can be flipped simply by changing the nature of the codon usage. Even expression of a luciferase reporter could be made Rev dependent or ORF57 dependent by distinctive changes to its codon usage. Our findings point to a new general principle in which different families of persisting viruses use a poor codon usage that is skewed in a distinctive way to temporally regulate late expression of structural gene products.
codon usage, SIV Rev, RRV ORF57, glycoprotein induction, temporal regulation
1Y.C.S. and G.F.B. contributed equally to this work.
2To whom correspondence should be addressed.
Author contributions: Y.C.S., G.F.B., and R.C.D. designed research; Y.C.S., G.F.B., and W.A.L. performed research; Y.C.S., G.F.B., W.A.L., and R.C.D. analyzed data; and Y.C.S. and R.C.D. wrote the paper.