Porcine endogenous retrovirus-A/C: biochemical properties of its integrase and susceptibility to raltegravir
Résumé
Porcine endogenous retroviruses (PERVs) are present in the genomes of pig cells. The PERV-A/C recombinant virus can infect human cells and is a major risk of zoonotic disease in the case of xenotransplantation of pig organs to humans. Raltegravir (RAL) is a viral integrase (IN) inhibitor used in highly active antiretroviral treatment. In the present study, we explored the potential use of RAL against PERV-A/C. We report (i) a three-dimensional model of the PERV-A/C intasome complexed with RAL, (ii) the sensitivity of PERV-A/C IN to RAL in vitro and (iii) the sensitivity of a PERV-A/C-IRES-GFP recombinant virus to RAL in cellulo. We demonstrated that RAL is a potent inhibitor against PERV-A/C IN and PERV-A/C replication with IC50s in the nanomolar range. To date, the use of retroviral inhibitors remains the only way to control the risk of zoonotic PERV infection during pig-to-human xenotransplantation.
Mots clés
Virus Integration/*drug effects
Swine
Raltegravir Potassium/chemistry/*pharmacology
Integrases/*analysis/chemistry
Inhibitory Concentration 50
Animals
Protein Binding
Protein Conformation
Crystallography
X-Ray
Antiviral Agents/chemistry/*pharmacology
Endogenous Retroviruses/drug effects/*enzymology/*physiology