Porcine endogenous retrovirus-A/C: biochemical properties of its integrase and susceptibility to raltegravir.
- Resource Type
- Academic Journal
- Authors
- Demange A; ANSES, Ploufragan/Plouzané Laboratory, Viral Genetics and Bio-Security Unit, Université Européenne de Bretagne, Ploufragan, France.; Yajjou-Hamalian H; 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.; Gallay K; 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.; Luengo C; 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.; Beven V; ANSES, Ploufragan/Plouzané Laboratory, Viral Genetics and Bio-Security Unit, Université Européenne de Bretagne, Ploufragan, France.; Leroux A; ANSES, Ploufragan/Plouzané Laboratory, Viral Genetics and Bio-Security Unit, Université Européenne de Bretagne, Ploufragan, France.; Confort MP; 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.; Al Andary E; 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.; Gouet P; 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.; Moreau K; 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.; Ronfort C; 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.; Blanchard Y; ANSES, Ploufragan/Plouzané Laboratory, Viral Genetics and Bio-Security Unit, Université Européenne de Bretagne, Ploufragan, France.
- Source
- Publisher: Microbiology Society Country of Publication: England NLM ID: 0077340 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1465-2099 (Electronic) Linking ISSN: 00221317 NLM ISO Abbreviation: J Gen Virol Subsets: MEDLINE
- Subject
- Language
- English
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.