title: Discovery of naturally occurring transmissible chronic hepatitis B virus infection among Macaca fascicularis from Mauritius Island.
abstract: Despite a high prevalence of hepatitis B virus (HBV) infection in endangered apes, no HBV infection has been reported in small, old-world monkeys. In search for a small, nonhuman primate model, we investigated the prevalence of HBV infection in 260 macaque (Cercopithecidae) sera of various geographical origins (i.e., Morocco, Mauritius Island, and Asia). HBV-positive markers were detected in cynomolgus macaques (Macaca fascicularis) from Mauritius Island only, and, remarkably, HBV DNA was positive in 25.8% (31 of 120) and 42% (21 of 50) of serum and liver samples, respectively. Strong liver expression of hepatitis B surface antigen and hepatitis B core antigen was detected in approximately 20%-30% of hepatocytes. Furthermore, chronic infection with persisting HBV DNA was documented in all 6 infected macaques during an 8-month follow-up period. Whole HBV genome-sequencing data revealed that it was genotype D subtype ayw3 carrying substitution in position 67 of preS1. To confirm infectivity of this isolate, 3 Macaca sylvanus were inoculated with a pool of M. fascicularis serum and developed an acute HBV infection with 100% sequence homology, compared with HBV inoculum. We demonstrated the presence of a chronic HBV infection in M. fascicularis from Mauritius Island. This closely human-related HBV might have been transmitted from humans, because the initial breeding colony originated from very few ancestors 300 years ago when it was implemented by Portuguese who imported a handful of macaques from Java to Mauritius Island.
  
  
  CONCLUSIONS
  This report on natural, persisting HBV infection among cynomolgus macaques provides the first evidence for the existence of a novel, small simian model of chronic HBV infection, immunologically close to humans, that should be most valuable for the study of immunotherapeutic approaches against chronic hepatitis B.
authors.affiliation: Université de Lyon, Lyon, France; INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France; CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France; Ecole pratique des hautes études, Paris, France.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Dupinay
authors.forename: Tarik
authors.initials: T
authors.lastname: Gheit
authors.forename: Pierre
authors.initials: P
authors.lastname: Roques
authors.forename: Lucyna
authors.initials: L
authors.lastname: Cova
authors.forename: Philippe
authors.initials: P
authors.lastname: Chevallier-Queyron
authors.forename: Shin-i
authors.initials: SI
authors.lastname: Tasahsu
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
authors.forename: François
authors.initials: F
authors.lastname: Simon
authors.forename: Geneviève
authors.initials: G
authors.lastname: Cordier
authors.forename: Lahcen
authors.initials: L
authors.lastname: Wakrim
authors.forename: Soumaya
authors.initials: S
authors.lastname: Benjelloun
authors.forename: Christian
authors.initials: C
authors.lastname: Trépo
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chemin
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D005838:Genotype; D019694:Hepatitis B, Chronic / Q000635:transmission / Q000662:veterinary*; D008252:Macaca fascicularis; D008436:Mauritius; D008969:Molecular Sequence Data; D008992:Monkey Diseases / Q000635:transmission*; D010802:Phylogeny
chemical_list: D000410:Alanine Transaminase