# The Cap-Independent Translation of Survivin 5′UTR and HIV-1 IRES Sequences Is Inhibited by Oxidative Stress Produced by H. pylori Gamma-Glutamyl Transpeptidase Activity

## TL;DR

This study shows that oxidative stress from H. pylori reduces the cap-independent translation of Survivin and HIV-1 IRES sequences.

## Contribution

The study reveals a novel GGT-dependent mechanism by which H. pylori inhibits cap-independent translation through oxidative stress.

## Key findings

- The short Survivin 5′UTR supports cap-independent translation similar to HIV-1 IRES.
- H. pylori infection inhibits this translation in a GGT-dependent manner in gastric cells.
- Oxidative stress from ATO treatment also reduces cap-independent translation.

## Abstract

Background: Survivin is an anti-apoptotic protein highly expressed during embryonic development and, in adults, mainly in the gastrointestinal epithelium. Its levels decrease in human gastric tissue and cultured cells upon exposure to Helicobacter pylori gamma-glutamyl transpeptidase (GGT), though the underlying mechanism remains unclear. Objective: We aimed to investigate the role of cap-independent translation driven by the Survivin 5′ untranslated region (5′UTR) in response to H. pylori infection in vitro. Methodology: Human cell lines (AGS, GES-1, HeLa, HEK293T) were used alongside bicistronic and monocistronic (Firefly/Renilla luciferases) reporter assays to assess short and long variants of the Survivin 5′UTR and HIV-1 internal ribosome entry site (IRES) sequences. Additional methods included in vitro transcription/translation, RT-qPCR, agarose gel electrophoresis, Western blotting, coupled/uncoupled translation assays, and siRNA silencing. Results: The short variant of the Survivin 5′ UTR supported cap-independent translation, like the HIV-1 IRES. Notably, H. pylori infection suppressed this translation in a GGT-dependent manner in gastric cells, and a similar reduction was observed following treatment with ATO, a known prooxidant. Conclusion: The Survivin 5′UTR exhibits cap-independent translation activity that is inhibited by H. pylori in a GGT-dependent manner, likely via oxidative stress. This mechanism helps to explain the downregulation of Survivin during gastric infection and indicates that oxidative stress can negatively affect both cellular and viral IRES-mediated translation.