Community Research and Development Information Service - CORDIS

FP7

DEGRAVIR Result In Brief

Project ID: 622142
Funded under: FP7-PEOPLE
Country: France

Viral hijack on host RNA

European researchers investigated the mechanisms by which viruses evade host immune responses. They discovered a novel viral protein-based pathway that allows viruses to suppress RNA degradation.
Viral hijack on host RNA
Viruses mediate infection by hijacking the host cellular machinery to replicate and suppress host defence responses, allowing viruses to thrive. Recent evidence suggests that viruses can evade host defence by integrating into RNA decay machineries, a key component of gene expression regulation. These mechanisms include de-capping, de-adenylation or nonsense-mediated decay (NMD) and they alter mRNA stability and degradation.

To investigate this possibility, scientists of the EU-funded DEGRAVIR (Suppression of RNA degradation by plant pararetrovirus: hijacking of decapping complexes) project utilised Cauliflower mosaic virus (CaMV) as a model system. They studied the role of the CaMV transactivator/ viroplasmin (TAV) protein, a multi-functional component known for its ability to overcome cellular barriers to polycistronic translation in eukaryotes.

Researchers discovered that TAV functioned as a suppressor of cellular mRNA turnover, by stabilising mRNAs that harbour premature stop codons that would normally get degraded via NMD mechanisms. Intriguingly, CaMV could recognise and stabilise such RNAs with internal termination codons and evade this host RNA quality control mechanism.

Further insight into the TAV mechanism indicated an interaction with the de-capping machinery via binding of the scaffold protein Varicose. The motif responsible for TAV function in NMD suppression was found to be remarkably conserved between CaMV and other related pararetroviruses.

Overall, the DEGRAVIR study provided fundamental information on how mRNA degradation pathways are involved in antiviral defence and how viruses directly suppress NMD to cause infection. Even though the present findings were derived from experiments in plant viruses, they could be extended to animal retroviruses with significant clinical ramifications.

Related information

Keywords

Virus, nonsense-mediated decay, DEGRAVIR, CaMV, TAV
Record Number: 191197 / Last updated on: 2017-02-23