[13] Overall, however, Old World monkeys have, so far, not been relevant as animal models in experimental HBV research, and, with the exception of chimpanzees, animal models with robust persistent infection remain unavailable. Human HBV or HBV variants closely related to human HBV have been isolated from greater (orangutan, gorilla, and chimpanzees) and lesser apes (gibbons), as reviewed previously.[14] In this

issue of HEPATOLOGY, an interesting study by Dupinay et al. describes the discovery of human Pritelivir ic50 HBV in cynomolgus monkeys of the species M. fascicularis on Mauritius Island.[15] This species of Old World monkeys, also called crab-eating or long-tailed macaque, was originally brought from Java to Mauritius Island,

located in the Indian Ocean east of Madagascar, off the South East coast of Africa (Fig. 1). Amazingly, the investigators found that approximately 25% of the tested monkeys were positive for HBV DNA check details in serum; HBsAg expression was detected in hepatocytes. However, many of the animals had what appeared to be occult low-titer HBV infections. More important, persistence of HBV DNA in serum was demonstrated in 6 animals followed for up to 8 months, thus providing evidence of persistent HBV infection. The HBV DNA titers in these particular animals were similar to titers reported in HBV chronically infected chimpanzees.[8] Furthermore, the virus was transmissible to naïve monkeys (M. sylvanus), with the appearance of HBV DNA and HBsAg markers and evidence of acute hepatitis; transmission to M. fascicularis monkeys was apparently not attempted. Finally, sequence analysis of HBV genomes of viruses recovered from M. fascicularis revealed that animals were infected Montelukast Sodium with human HBV genotype D; genotype D is a

common HBV genotype found worldwide. The recovered viruses did have potentially important mutations, compared with HBV currently circulating in humans, which could perhaps explain permissiveness in Old World monkeys. The major obstacle for translating this novel finding of persistent human HBV infection in macaques into an available animal model is the establishment of persistent experimental infections. This could involve neonatal infections and/or immunosuppression. However, such approaches did not result in persistent experimental infections of Woolly monkey HBV in spider monkeys.[10] It would be relevant to test different Old World monkey species for susceptibility to this human HBV variant. This research could involve the generation of molecular clones representing the exact HBV variant identified in cynomolgus monkeys on Mauritius Island, or cloned human HBV with the insertion of specific identified mutations, such as a unique substitution identified in the pre-S1 domain of the L glycoprotein involved with receptor binding.