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
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 : Thursday, February 20, 2020 - 7:23:48 PM

Links full text

openaccess

Identifiers

Collections

UNIV-LYON1 | IVPC | INRA | EPHE | PSL | UDL

Citation

A. Demange, Halima Yajjou-Hamalian, Kathy Gallay, Catherine Luengo, V. Beven, et al.. Porcine endogenous retrovirus-A/C: biochemical properties of its integrase and susceptibility to raltegravir. Journal of General Virology, 2015, 96 (10), pp.3124-30. ⟨10.1099/jgv.0.000236⟩. ⟨hal-02192915⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

23

Contact

Informations

CCSD