Hepatitis C virus infects rhesus macaque hepatocytes and simianized mice. Author Margaret Scull, Chao Shi, Ype de Jong, Gisa Gerold, Moritz Ries, Markus von Schaewen, Bridget Donovan, Rachael Labitt, Joshua Horwitz, Jenna Gaska, Gabriela Hrebikova, Jing Xiao, Brenna Flatley, Canny Fung, Luis Chiriboga, Christopher Walker, David Evans, Charles Rice, Alexander Ploss Publication Year 2015 Type Journal Article Abstract UNLABELLED: At least 170 million people are chronically infected with hepatitis C virus (HCV). Owing to the narrow host range of HCV and restricted use of chimpanzees, there is currently no suitable animal model for HCV pathogenesis studies or the development of a HCV vaccine. To identify cellular determinants of interspecies transmission and establish a novel immunocompetent model system, we examined the ability of HCV to infect hepatocytes from a small nonhuman primate, the rhesus macaque (Macaca mulatta). We show that the rhesus orthologs of critical HCV entry factors support viral glycoprotein-dependent virion uptake. Primary hepatocytes from rhesus macaques are also permissive for HCV-RNA replication and particle production, which is enhanced when antiviral signaling is suppressed. We demonstrate that this may be owing to the diminished capacity of HCV to antagonize mitochondrial antiviral-signaling protein-dependent innate cellular defenses. To test the ability of HCV to establish persistent replication in vivo, we engrafted primary rhesus macaque hepatocytes into immunocompromised xenorecipients. Inoculation of resulting simian liver chimeric mice with either HCV genotype 1a or 2a resulted in HCV serum viremia for up to 10 weeks.CONCLUSION: Together, these data indicate that rhesus macaques may be a viable model for HCV and implicate host immunity as a potential species-specific barrier to HCV infection. We conclude that suppression of host immunity or further viral adaptation may allow robust HCV infection in rhesus macaques and creation of a new animal model for studies of HCV pathogenesis, lentivirus coinfection, and vaccine development. Keywords Animals, Disease Models, Animal, Mice, Humans, Macaca mulatta, Virus Replication, Hepacivirus, Hepatitis C, Hepatocytes, Host-Pathogen Interactions, Immunity, Innate, Virus Internalization Journal Hepatology Volume 62 Issue 1 Pages 57-67 Date Published 2015 Jul ISSN Number 1527-3350 DOI 10.1002/hep.27773 Alternate Journal Hepatology PMCID PMC4482775 PMID 25820364 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML