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

A. Demange; Halima Yajjou-Hamalian; Kathy Gallay; Catherine Luengo; V. Beven; A. Leroux; Marie-Pierre Confort; Elsy Al Andary; P. Gouet; Karen Moreau; Corinne Ronfort; Y. Blanchard

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

A. Demange Halima Yajjou-Hamalian ¹ Kathy Gallay ¹ Catherine Luengo ¹ V. Beven A. Leroux Marie-Pierre Confort ¹ Elsy Al Andary ¹ P. Gouet Karen Moreau ¹ Corinne Ronfort ¹ Y. Blanchard

1 IVPC - Infections Virales et Pathologie Comparée - UMR 754

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.

Keywords : Animals Protein Binding Protein Conformation Crystallography X-Ray Antiviral Agents/chemistry/*pharmacology Endogenous Retroviruses/drug effects/*enzymology/*physiology Inhibitory Concentration 50 Integrases/*analysis/chemistry Raltegravir Potassium/chemistry/*pharmacology Swine Virus Integration/*drug effects

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Complete list of metadatas

https://hal-univ-lyon1.archives-ouvertes.fr/hal-02192915
Contributor : Marie-Gabrielle Chautard <>
Submitted on : Wednesday, July 24, 2019 - 10:55:33 AM
Last modification on : Tuesday, September 24, 2019 - 4:23:47 PM

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

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

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