The Highly Conserved Codon following the Slippery Sequence Supports -1 Frameshift Efficiency at the HIV-1 Frameshift Site

Mathew, Suneeth F.; Crowe-McAuliffe, Caillan; Graves, Ryan; Cardno, Tony S.; McKinney, Cushla; Poole, Elizabeth S.; Tate, Warren P.

Despite the error-prone nature of HIV replication, the frameshift element encompassing the slippery sequence and the stem-loop structural feature in the mRNA is highly conserved among HIV-1 sequences derived from patient blood samples [49] , [50] . This observation is consistent with functional studies demonstrating that mutations perturbing −1 PRF dramatically effect replication efficiency of HIV-1. Moreover, recent observations indicate that only those mRNAs undergoing frameshifting are packaged into nascent HIV-1 virus particles, emphasising the importance of the PRF element [51] , [52] . The conserved consensus sequence of the −1 PRF element of HIV-1 is shown in Fig. 1A . In an alignment of 3534 HIV-1 sequences, derived mostly from patient blood samples, we noted the intercodon following the slippery sequence was almost as highly conserved as the slippery sequence itself (Fig. 1B) . Although minor variation was observed at the third position of the intercodon, 94.7% of sequences listed were GGG with G in this third position. The next most common codon was GGA (4.2%), and GGC was the only other codon with significant frequency (0.8%) (Fig. 1B) . The remaining 0.3% may represent 'noise' from non-functional sequences not detected by the exclusion criteria. The consensus −1 PRF element derived from these data is shown in Fig. 1C .