title: 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: ANSES, Ploufragan/Plouzané Laboratory, Viral Genetics and Bio-Security Unit, Université Européenne de Bretagne, Ploufragan, France.
authors: Antonin
authors: A
authors: Demange
authors: Institut de Biologie et Chimie des Protéines, BMSSI-IBCP, UMR 5086 CNRS Université Lyon 1, 7, passage du Vercors, 69367 Lyon Cedex 07, France.|INRA, Université Lyon 1, UMR754, Rétrovirus et Pathologie Comparée, 69007 Lyon, France.|Université de Lyon, 69000 Lyon, France.|UMS3444 BioSciences Gerland Lyon Sud, 69007 Lyon, France.
authors: Halima
authors: H
authors: Yajjou-Hamalian
authors: INRA, Université Lyon 1, UMR754, Rétrovirus et Pathologie Comparée, 69007 Lyon, France.|Université de Lyon, 69000 Lyon, France.|UMS3444 BioSciences Gerland Lyon Sud, 69007 Lyon, France.
authors: Kathy
authors: K
authors: Gallay
authors: INRA, Université Lyon 1, UMR754, Rétrovirus et Pathologie Comparée, 69007 Lyon, France.|UMS3444 BioSciences Gerland Lyon Sud, 69007 Lyon, France.|Université de Lyon, 69000 Lyon, France.
authors: Catherine
authors: C
authors: Luengo
authors: ANSES, Ploufragan/Plouzané Laboratory, Viral Genetics and Bio-Security Unit, Université Européenne de Bretagne, Ploufragan, France.
authors: Véronique
authors: V
authors: Beven
authors: ANSES, Ploufragan/Plouzané Laboratory, Viral Genetics and Bio-Security Unit, Université Européenne de Bretagne, Ploufragan, France.
authors: Aurélie
authors: A
authors: Leroux
authors: INRA, Université Lyon 1, UMR754, Rétrovirus et Pathologie Comparée, 69007 Lyon, France.|Université de Lyon, 69000 Lyon, France.|UMS3444 BioSciences Gerland Lyon Sud, 69007 Lyon, France.
authors: Marie-Pierre
authors: MP
authors: Confort
authors: ANSES, Ploufragan/Plouzané Laboratory, Viral Genetics and Bio-Security Unit, Université Européenne de Bretagne, Ploufragan, France.|Université de Lyon, 69000 Lyon, France.|UMS3444 BioSciences Gerland Lyon Sud, 69007 Lyon, France.|INRA, Université Lyon 1, UMR754, Rétrovirus et Pathologie Comparée, 69007 Lyon, France.
authors: Elsy
authors: E
authors: Al Andary
authors: Université de Lyon, 69000 Lyon, France.|UMS3444 BioSciences Gerland Lyon Sud, 69007 Lyon, France.|Institut de Biologie et Chimie des Protéines, BMSSI-IBCP, UMR 5086 CNRS Université Lyon 1, 7, passage du Vercors, 69367 Lyon Cedex 07, France.
authors: Patrice
authors: P
authors: Gouet
authors: Université de Lyon, 69000 Lyon, France.|INRA, Université Lyon 1, UMR754, Rétrovirus et Pathologie Comparée, 69007 Lyon, France.|UMS3444 BioSciences Gerland Lyon Sud, 69007 Lyon, France.
authors: Karen
authors: K
authors: Moreau
authors: UMS3444 BioSciences Gerland Lyon Sud, 69007 Lyon, France.|INRA, Université Lyon 1, UMR754, Rétrovirus et Pathologie Comparée, 69007 Lyon, France.|Université de Lyon, 69000 Lyon, France.
authors: Corinne
authors: C
authors: Ronfort
authors: ANSES, Ploufragan/Plouzané Laboratory, Viral Genetics and Bio-Security Unit, Université Européenne de Bretagne, Ploufragan, France.
authors: Yannick
authors: Y
authors: Blanchard
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D020077:Endogenous Retroviruses / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D020128:Inhibitory Concentration 50; D019426:Integrases / Q000032:analysis* / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D000068898:Raltegravir Potassium / Q000737:chemistry / Q000494:pharmacology*; D013552:Swine; D016662:Virus Integration / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D000068898:Raltegravir Potassium; D019426:Integrases