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Updated: Apr 15, 2026

Amplification of Near Full-length HIV-1 Proviruses for Next-Generation Sequencing
Published on: October 16, 2018
The highly conserved codon following the slippery sequence supports -1 frameshift efficiency at the HIV-1 frameshift
Suneeth F Mathew1, Caillan Crowe-McAuliffe1, Ryan Graves1
1Department of Biochemistry, University of Otago, Dunedin, 9054, New Zealand.
Abstract:
HIV-1 utilises -1 programmed ribosomal frameshifting to translate structural and enzymatic domains in a defined proportion required for replication. A slippery sequence, U UUU UUA, and a stem-loop are well-defined RNA features modulating -1 frameshifting in HIV-1. The GGG glycine codon immediately following the slippery sequence (the 'intercodon') contributes structurally to the start of the stem-loop but has no defined role in current models of the frameshift mechanism, as slippage is inferred to occur before the intercodon has reached the ribosomal decoding site. This GGG codon is highly conserved in natural isolates of HIV. When the natural intercodon was replaced with a stop codon two different decoding molecules-eRF1 protein or a cognate suppressor tRNA-were able to access and decode the intercodon prior to -1 frameshifting. This implies significant slippage occurs when the intercodon is in the (perhaps distorted) ribosomal A site. We accommodate the influence of the intercodon in a model of frame maintenance versus frameshifting in HIV-1.
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