title: Experimental transfection of Macaca sylvanus with cloned human hepatitis B virus.
abstract: Due to the absence of easily accessible animal models for the study of hepatitis B virus (HBV), the possibility of using Macaca sylvanus, a monkey originating from Morocco, North Africa, was investigated. Three monkeys were intrahepatically inoculated with a replication-competent head-to-tail HBV DNA plasmid dimer construct. The HBV surface antigen and HBV DNA were detected prior to alanine aminotransferase elevation in the serum of two of three HBV-inoculated monkeys at day 2 post-transfection and persisted for several weeks. This indicates that transfected animals developed markers of HBV infection. In addition, electron microscopy of the serum 3 weeks post-transfection showed the presence of virus particles whose shape and size were similar to complete 42 nm HBV Dane particles. Histological examination of liver tissues also revealed pathological changes not observed in uninfected controls, which strongly suggested acute hepatitis. HBV DNA was also detected by PCR in these monkey livers. Taken together, these results indicate that HBV can successfully replicate in this model and that M. sylvanus could be a potentially useful new primate model for the study of HBV replication.
authors.affiliation: Unité de recherche sur les virus des hépatites et pathologies associées, Institut national de la santé et de la recherche médicale 271, 69424 Lyon Cedex 03, France1.
authors.forename: Tarik
authors.initials: T
authors.lastname: Gheit
authors.affiliation: Centre d'immunologie, Faculté de Médecine et Pharmacie, BP 9154, Casablanca, Morocco2.
authors.forename: Souad
authors.initials: S
authors.lastname: Sekkat
authors.affiliation: Unité de recherche sur les virus des hépatites et pathologies associées, Institut national de la santé et de la recherche médicale 271, 69424 Lyon Cedex 03, France1.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Cova
authors.affiliation: Laboratoire d'anatomie et de cytologie pathologiques, Laboratoire Marcel Mérieux, 69365 Lyon Cedex 07, France3.
authors.forename: Michèle
authors.initials: M
authors.lastname: Chevallier
authors.affiliation: Unité de recherche sur les virus des hépatites et pathologies associées, Institut national de la santé et de la recherche médicale 271, 69424 Lyon Cedex 03, France1.
authors.forename: Marie Anne
authors.initials: MA
authors.lastname: Petit
authors.affiliation: Unité de recherche sur les virus des hépatites et pathologies associées, Institut national de la santé et de la recherche médicale 271, 69424 Lyon Cedex 03, France1.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hantz
authors.affiliation: bioMérieux, Marcy l'étoile 69280, France4.
authors.forename: Mylène
authors.initials: M
authors.lastname: Lesénéchal
authors.affiliation: Centre d'immunologie, Faculté de Médecine et Pharmacie, BP 9154, Casablanca, Morocco2.
authors.forename: Abdallah
authors.initials: A
authors.lastname: Benslimane
authors.affiliation: Unité de recherche sur les virus des hépatites et pathologies associées, Institut national de la santé et de la recherche médicale 271, 69424 Lyon Cedex 03, France1.
authors.forename: Christian
authors.initials: C
authors.lastname: Trépo
authors.affiliation: Unité de recherche sur les virus des hépatites et pathologies associées, Institut national de la santé et de la recherche médicale 271, 69424 Lyon Cedex 03, France1.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chemin
mesh_terms: D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015139:Blotting, Southern; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D005822:Genetic Vectors; D006509:Hepatitis B / Q000276:immunology / Q000821:virology*; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000473:pathology / Q000821:virology; D008251:Macaca; D008854:Microscopy, Electron; D010957:Plasmids; D016133:Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
chemical_list: D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D000410:Alanine Transaminase