Citation: Capozza, P.; Carrai, M.; Choi, Y.R.; Tu, T.; Nekouei, O.; Lanave, G.; Martella, V.; Beatty, J.A.; Barrs, V.R. Domestic Cat Hepadnavirus: Molecular Epidemiology and Phylogeny in Cats in Hong Kong. Viruses 2023, 15, 150. https://doi.org/10.3390/v15010150 Academic Editor: Ayato Takada Received: 22 December 2022 Revised: 30 December 2022 Accepted: 31 December 2022 Published: 3 January 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). viruses Article Domestic Cat Hepadnavirus: Molecular Epidemiology and Phylogeny in Cats in Hong Kong Paolo Capozza 1,† , Maura Carrai 2,3,† , Yan Ru Choi 2,3,† , Thomas Tu 4,5 , Omid Nekouei 6 , Gianvito Lanave 1 , Vito Martella 1 , Julia A. Beatty 2,3, * and Vanessa R. Barrs 2,3, * 1 Department of Veterinary Medicine, University of Bari Aldo Moro, 70010 Valenzano, Italy 2 Department of Veterinary Clinical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong 3 Centre for Animal Health and Welfare, City University of Hong Kong, Kowloon Tong, Hong Kong 4 Storr Liver Centre, Westmead Clinical School and Westmead Institute for Medical Research, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia 5 Sydney Institute for Infectious Diseases, University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia 6 Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong * Correspondence: julia.beatty@cityu.edu.hk (J.A.B.); vanessa.barrs@cityu.edu.hk (V.R.B.) † These authors contributed equally to this work. Abstract: Domestic cat hepadnavirus (DCH) is an emerging virus related to the hepatitis B virus (HBV). The pathogenic potential of DCH in cats remains to be established. The molecular prevalence of DCH varies widely in the regions investigated so far. The aim of this study was to determine the prevalence, load, and risk factors for DCH detection among cats in Hong Kong, and to generate molecular and epidemiological data on the DCH strains circulating in cats in Hong Kong. DCH DNA was detected using DCH-specific qPCR in 57/513 (11.1%) residual diagnostic blood samples from owned cats. The median viral load was 8.85 × 10 3 copies/mL of whole blood (range for the 5th to the 95th percentile, 3.33 × 10 3 to 2.2 × 10 5 copies per mL). Two outliers had higher viral loads of 1.88 × 10 7 copies/mL and 4.90 × 10 9 copies/mL. DCH was detected in cats from 3 months to 19 years of age. Sex, age, neuter status, breed, or elevated serum alanine aminotransferase were not statistically associated with DCH DNA detection. On phylogenetic analysis based on 12 complete genome sequences, the Hong Kong DCH viruses clustered in Genotype A with viruses from Australia and Asia (clade A1), distinct from viruses from Europe (clade A2). Sequence analysis found that DCH has similar epsilon and direct repeat regions to human HBV, suggesting a conserved method of replication. Based on our findings, the DCH strains circulating in Hong Kong are a continuum of the Asiatic strains. Keywords: cat; hepadnavirus; liver; hepatitis; viral; cancer; hepatitis B 1. Introduction Domestic cat hepadnavirus (DCH) is a newly discovered virus in the Hepadnaviridae, a family of over 17 species of partially double-stranded DNA viruses containing five genera of viruses infecting mammals (Genus Orthohepadnavirus), fish (Genus Metahepadnavirus and Parahepadnavirus), amphibians, reptiles (Genus Herpetohepadnavirus), and birds (Genus Avihepadnavirus)[1]. Orthohepadnaviruses cause varying degrees of liver pathology in their hosts. The prototype species, hepatitis B virus (HBV), is a major human pathogen. In 2019, an estimated 316 million people were living with chronic HBV infection [2], of whom >550,000 people died from liver cirrhosis and hepatocellular carcinoma (HCC) [3,4]. In woodchucks chronically infected with woodchuck hepatitis virus (WHV), hepatocellular carcinoma is almost inevitable with the lifetime risk approaching 100% [5]. Viruses 2023, 15, 150. https://doi.org/10.3390/v15010150 https://www.mdpi.com/journal/viruses