HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome

Mouzakis, Kathryn D.; Lang, Andrew L.; Vander Meulen, Kirk A.; Easterday, Preston D.; Butcher, Samuel E.

Translation is a high-fidelity process in all organisms. Failure to maintain reading frame typically results in incorrect protein synthesis and/or early termination. However, a programmed change in reading frame can result in the translation of new proteins, thereby maximizing genomic coding capacity. Many retroviruses, including human immunodeficiency virus type 1 (HIV-1) (1) , and some coronaviruses, such as severe acute respiratory syndrome (2) and infectious bronchitis virus (IBV) (3), use a programmed À1 ribosomal frameshift (À1 PRF) to control translation levels of their enzymatic proteins (4) (5) (6) (7) . In the retroviruses, the À1 PRF site lies between the gag and pol open reading frames (ORFs), with pol in the À1 reading frame relative to gag. The gag ORF encodes the viral structural proteins, whereas the pol ORF encodes the enzymatic proteins. During translation of HIV-1 mRNA, the majority of ribosomes terminate at a stop codon at the end of the gag ORF, producing the Gag polyprotein (2, 8) . However, the HIV À1 PRF induces $5% of ribosomes to shift into the À1 reading frame, thus producing the Gag-Pol polyprotein (1, (9) (10) (11) . The 5% frameshift efficiency determines the ratio of viral proteins produced and is important for viral replication and infectivity (10, (12) (13) (14) (15) . A decrease in frameshift efficiency can inhibit viral replication (16, 17) .