Ribonuclease zymogen induces cytotoxicity upon HIV-1 infection.

ABSTRACT:

Background

Targeting RNA is a promising yet underdeveloped modality for the selective killing of cells infected with HIV-1. The secretory ribonucleases (RNases) found in vertebrates have cytotoxic ribonucleolytic activity that is kept in check by a cytosolic ribonuclease inhibitor protein, RI.

Methods

We engineered amino acid substitutions that enable human RNase 1 to evade RI upon its cyclization into a zymogen that is activated by the HIV-1 protease. In effect, the zymogen has an HIV-1 protease cleavage site between the termini of the wild-type enzyme, thereby positioning a cleavable linker over the active site that blocks access to a substrate.

Results

The amino acid substitutions in RNase 1 diminish its affinity for RI by 10⁶-fold and confer high toxici

SUBMITTER: Windsor IW 

PROVIDER: S-EPMC8549155 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature