Experimental transfection of Macaca sylvanus with cloned human hepatitis B virus.
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.
Gheit
Tarik
T
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.
Sekkat
Souad
S
Centre d'immunologie, Faculté de Médecine et Pharmacie, BP 9154, Casablanca, Morocco2.
Cova
Lucyna
L
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.
Chevallier
Michèle
M
Laboratoire d'anatomie et de cytologie pathologiques, Laboratoire Marcel Mérieux, 69365 Lyon Cedex 07, France3.
Petit
Marie Anne
MA
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.
Hantz
Olivier
O
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.
Lesénéchal
Mylène
M
bioMérieux, Marcy l'étoile 69280, France4.
Benslimane
Abdallah
A
Centre d'immunologie, Faculté de Médecine et Pharmacie, BP 9154, Casablanca, Morocco2.
Trépo
Christian
C
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.
Chemin
Isabelle
I
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.
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
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D000410:Alanine Transaminase