Viruses, Vol. 16, Pages 583: The Inhibition of Gag-Pol Expression by the Restriction Factor Shiftless Is Dispensable for the Restriction of HIV-1 Infection

Viruses, Vol. 16, Pages 583: The Inhibition of Gag-Pol Expression by the Restriction Factor Shiftless Is Dispensable for the Restriction of HIV-1 Infection
Viruses doi: 10.3390/v16040583
Authors:
Niklas Jäger
Shreya Ahana Ayyub
Frank Peske
David Liedtke
Jens Bohne
Markus Hoffmann
Marina V. Rodnina
Stefan Pöhlmann

The interferon-induced host cell protein Shiftless (SFL) inhibits −1 programmed ribosomal frameshifting (−1PRF) required for the expression of HIV-1 Gal-Pol and the formation of infectious HIV-1 particles. However, the specific regions in SFL required for antiviral activity and the mechanism by which SFL inhibits −1PRF remain unclear. Employing alanine scanning mutagenesis, we found that basic amino acids in the predicted zinc ribbon motif of SFL are essential for the suppression of Gag-Pol expression but dispensable for anti-HIV-1 activity. We have shown that SFL inhibits the expression of the murine leukemia virus (MLV) Gag-Pol polyprotein and the formation of infectious MLV particles, although Gag-Pol expression of MLV is independent of −1PRF but requires readthrough of a stop codon. These findings indicate that SFL might inhibit HIV-1 infection by more than one mechanism and that SFL might target programmed translational readthrough as well as −1PRF signals, both of which are regulated by mRNA secondary structure elements.

Source: Viruses - April 10, 2024 Category: Virology Authors: Niklas J äger Shreya Ahana Ayyub Frank Peske David Liedtke Jens Bohne Markus Hoffmann Marina V. Rodnina Stefan P öhlmann Tags: Article Source Type: research