Porcine endogenous retrovirus-A/C: biochemical properties of its integrase and susceptibility to raltegravir.

Abstract

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.

• Authors: Antonin Demange, Halima Yajjou-Hamalian, Kathy Gallay, Catherine Luengo, Véronique Beven, Aurélie Leroux, Marie-Pierre Confort, Elsy Al Andary, Patrice Gouet, Karen Moreau, Corinne Ronfort, Yannick Blanchard
• Journal: The Journal of general virology (J Gen Virol) Vol. 96 Issue 10 Pg. 3124-3130 (Oct 2015) ISSN: 1465-2099 [Electronic] England
• PMID: 26296914 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Raltegravir Potassium
• Integrases

Topics

• Animals
• Antiviral Agents (chemistry, pharmacology)
• Crystallography, X-Ray
• Endogenous Retroviruses (drug effects, enzymology, physiology)
• Inhibitory Concentration 50
• Integrases (analysis, chemistry)
• Protein Binding
• Protein Conformation
• Raltegravir Potassium (chemistry, pharmacology)
• Swine
• Virus Integration (drug effects)