biostudies-literatureXu ZFundamental Research Funds for the Central UniversitiesKey Technologies Research and Development ProgramBasic and Clinical Medical Research Joint Fund of Zhongnan Hospital, Wuhan UniversityPostdoctoral Research Foundation of ChinaHubei Province’s Outstanding Medical Academic Leader ProgramNational Natural Science Foundation of ChinaOpen Grant from the Pingyuan LaboratoryEast Lake Hi-tech Development Zone Unveiling and Commanding ProjectScience and Technology Talent Service Enterprise Projecte1013390https://www.ebi.ac.uk/biostudies/studies/S-EPMC12333979biostudies-literatureUnknown21(8)Hepatitis B virus (HBV) remains a major public health challenge, with nearly 300 million chronic infections, yet research is hindered by the lack of suitable animal models. This study aimed to identify HBV-susceptible species and establish a novel infection model. Primary hepatocytes from humans, cats, rabbits, Syrian hamsters, Siberian hamsters, guinea pigs, bulls, goats, pigs, cynomolgus macaques, and dogs were assessed for HBV entry using hepatitis D virus (HDV) infection. HBV relaxed circular DNA (rcDNA) transfection was performed to evaluate its repair into covalently closed circular DNA (cccDNA). HBV infection assays were conducted in vitro. Results showed that primary hepatocytes from humans and cats were susceptible to HDV, suggesting their potential to support HBV entry. All testePLoS pathogensScreening of different species reveals cat hepatocytes support HBV infection.PMC123339792023M7326952023PY-OP-01012023KJB2192042024kf00262024DJC06481971936321001252023YFC230850032300131Xia YChen NZhang LWang JCheng XZhu CWang MZhao GXin TZhao KChen SXu ZYin JfalseScreening of different species reveals cat hepatocytes support HBV infection.Hepatitis B virus (HBV) remains a major public health challenge, with nearly 300 million chronic infections, yet research is hindered by the lack of suitable animal models. This study aimed to identify HBV-susceptible species and establish a novel infection model. Primary hepatocytes from humans, cats, rabbits, Syrian hamsters, Siberian hamsters, guinea pigs, bulls, goats, pigs, cynomolgus macaques, and dogs were assessed for HBV entry using hepatitis D virus (HDV) infection. HBV relaxed circular DNA (rcDNA) transfection was performed to evaluate its repair into covalently closed circular DNA (cccDNA). HBV infection assays were conducted in vitro. Results showed that primary hepatocytes from humans and cats were susceptible to HDV, suggesting their potential to support HBV entry. All teste2025-01-01T00:00:00Z2025 Aug2026-04-15T19:10:54.688Z2026-04-07T14:00:55.918ZS-EPMC123339794075874110.1371/journal.ppat.1013390