Virological and pathological characterization of an outbreak of domestic cat hepatitis B virus infection in a cat shelter in Japan

Nanami X Kato; Haruka Dosaka; Yukinobu Adachi; Yasuyuki Kaneko; Takuya Hirai; Satoshi Sekiguchi; Naoyuki Fuke; Saito, Akatsuki

doi:10.51094/jxiv.2529

##article.authors##

Nanami X Kato Laboratory of Veterinary Microbiology, Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki
Haruka Dosaka Laboratory of Veterinary Pathology, Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki
Yukinobu Adachi Kaze Animal Hospital
Yasuyuki Kaneko Veterinary Teaching Hospital, Faculty of Agriculture, University of Miyazaki
Takuya Hirai Laboratory of Veterinary Pathology, Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki
Satoshi Sekiguchi Center for Animal Disease Control, University of Miyazaki
Naoyuki Fuke Laboratory of Veterinary Pathology, Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki
Saito, Akatsuki University of Miyazaki

DOI:

https://doi.org/10.51094/jxiv.2529

キーワード:

cat shelter、 domestic cat hepatitis B virus

抄録

Domestic cat hepatitis B virus (DCHBV) infections are associated with chronic hepatitis and hepatic

cancer in cats, similar to human HBV . We previously demonstrated that the positivity rate for DCHBV

in Japan is less than 1% among tested samples, suggesting lower viral dissemination in Japan than in

other countries. Furthermore, the transmission dynamics of DCHBV remain poorly understood. In this

study, we identified the first recorded outbreak of DCHBV within a cat shelter, with an

unprecedentedly high prevalence of 26.59% (46/173 cats). We investigated potential transmission

routes by performing quantitative polymerase chain reaction on matched blood, oral, and rectal swab

samples. We found a significant correlation between blood and oral viral loads, with viral DNA

detected in both oral (40.54%) and rectal (19.44%) cavities of viremic cats. Phylogenetic analysis of

the polymerase gene from deceased cats yielded >99.2% sequence identity, indicating the circulation

of a single strain. Pathological assessments, including histopathology, immunohistochemistry, and

RNA in situ hybridization, confirmed viral presence in hepatocytes and biliary epithelium, linking the

outbreak with severe hepatic lesions, including cholangitis, fibrosis, and cholangiocarcinoma. Our

findings indicate that the transmission route of DCHBV may be more complex than initially

anticipated, underscoring the importance of understanding the mode of transmission to effectively

control DCHBV infection, particularly in multi-cat facilities.

利益相反に関する開示

The authors declare no conflict of interest.

ダウンロード *前日までの集計結果を表示します

ダウンロード実績データは、公開の翌日以降に作成されます。

引用文献

Adıgüzel, E., Erdem-Şahinkesen, E., Koç, B. T., Demirden, C. and Oğuzoğlu, T. Ç. 2023. The detection and full genomic characterization of domestic cat Orthohepadnaviruses from Türkiye. Vet Med Sci. 9: 1965–1972.

Aghazadeh, M., Shi, M., Barrs, V. R., McLuckie, A. J., Lindsay, S. A., Jameson, B., Hampson, B., Holmes, E. C. and Beatty, J. A. 2018. A Novel Hepadnavirus Identified in an Immunocompromised Domestic Cat in Australia. Viruses. 10: 269.

Anpuanandam, K., Selvarajah, G. T., Choy, M. M. K., Ng, S. W., Kumar, K., Ali, R. M., Rajendran, S. K., Ho, K. L. and Tan, W. S. 2021. Molecular detection and characterisation of Domestic Cat Hepadnavirus (DCH) from blood and liver tissues of cats in Malaysia. BMC Vet Res. 17: 9.

Beasley, R. P., Hwang, L. Y., Lin, C. C. and Chien, C. S. 1981. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet. 2: 1129–1133.

Brechot, C., Pourcel, C., Louise, A., Rain, B. and Tiollais, P. 1980. Presence of integrated hepatitis B virus DNA sequences in cellular DNA of human hepatocellular carcinoma. Nature. 286: 533–535.

Capozza, P., Carrai, M., Choi, Y. R., Tu, T., Nekouei, O., Lanave, G., Martella, V., Beatty, J. A. and Barrs, V. R. 2023. Domestic Cat Hepadnavirus: Molecular Epidemiology and Phylogeny in Cats in Hong Kong. Viruses. 15: 150.

Cavasin, J. P., Chen, M.-C., Ajoyan, H., Dobromylskyj, M. J., Huang, W.-H., Jager, M., Van Brussel, K., Rockett, R., Nekouei, O., Watson, P., Bestwick, J., Choi, Y. R., Lidbury, J. A., Cullen, J. M., Holmes, E., Steiner, J. M., Tu, T. and Beatty, J. A. 2025. Recurrent integration of domestic cat hepatitis B virus DNA near feline CCNE1 supports an oncogenic role in hepatocellular carcinoma in cats. Tumour Virus Res. 20: 200324.

Diakoudi, G., Capozza, P., Lanave, G., Pellegrini, F., Di Martino, B., Elia, G., Decaro, N., Camero, M., Ghergo, P., Stasi, F., Cavalli, A., Tempesta, M., Barrs, V. R., Beatty, J., Bányai, K., Catella, C., Lucente, M. S., Buonavoglia, A., Fusco, G. and Martella, V. 2022. A novel hepadnavirus in domestic dogs. Sci Rep. 12: 2864.

Dosaka, H., Kato, N. X., Taga, K., Yamamoto, S., Kondo, K., Ringo, R. S., Kaneko, Y., Hirai, T., Saito, A. and Fuke, N. 2026. Distribution of domestic cat hepatitis B virus in cholangiocarcinoma and non-neoplastic liver tissue. J Vet Med Sci. (in press).

Fruci, P., Di Profio, F., Palombieri, A., Massirio, I., Lanave, G., Diakoudi, G., Pellegrini, F., Marsilio, F., Martella, V. and Di Martino, B. 2022. Detection of antibodies against domestic cat hepadnavirus using baculovirus-expressed core protein. Transbound Emerg Dis. 69: 2980–2986.

Heiberg, I. L., Hoegh, M., Ladelund, S., Niesters, H. G. M. and Hogh, B. 2010. Hepatitis B virus DNA in saliva from children with chronic hepatitis B infection: implications for saliva as a potential mode of horizontal transmission. Pediatr Infect Dis J. 29: 465–467.

Imazeki, F., Yaginuma, K., Omata, M., Okuda, K., Kobayashi, M. and Koike, K. 1988. Integrated structures of duck hepatitis B virus DNA in hepatocellular carcinoma. J Virol. 62: 861–865.

Jeanes, E. C., Wegg, M. L., Mitchell, J. A., Priestnall, S. L., Fleming, L. and Dawson, C. 2022. Comparison of the prevalence of Domestic Cat Hepadnavirus in a population of cats with uveitis and in a healthy blood donor cat population in the United Kingdom. Vet Ophthalmol. 25: 165–172.

Komatsu, H., Inui, A., Sogo, T., Tateno, A., Shimokawa, R. and Fujisawa, T. 2012. Tears from children with chronic hepatitis B virus (HBV) infection are infectious vehicles of HBV transmission: experimental transmission of HBV by tears, using mice with chimeric human livers. J Infect Dis. 206: 478–485.

Lanave, G., Capozza, P., Diakoudi, G., Catella, C., Catucci, L., Ghergo, P., Stasi, F., Barrs, V., Beatty, J., Decaro, N., Buonavoglia, C., Martella, V. and Camero, M. 2019. Identification of hepadnavirus in the sera of cats. Sci Rep. 9: 10668.

Lanford, R. E., Chavez, D., Brasky, K. M., Burns, R. B. and Rico-Hesse, R. 1998. Isolation of a hepadnavirus from the woolly monkey, a New World primate. Proc Natl Acad Sci U S A. 95: 5757–5761.

Lin, B., He, Q., Lu, Y., Zhang, W., Jin, J. and Pan, H. 2023. Viral hepatitis increases the risk of cholangiocarcinoma: a systematic review and meta-analysis. Transl Cancer Res. 12: 1602–1616.

Magnius, L., Mason, W. S., Taylor, J., Kann, M., Glebe, D., Dény, P., Sureau, C., Norder, H. and Ictv Report Consortium, null 2020. ICTV Virus Taxonomy Profile: Hepadnaviridae. J Gen Virol. 101: 571–572.

Mazzaro, C., Adinolfi, L. E., Pozzato, G., Nevola, R., Zanier, A., Serraino, D., Andreone, P., Fenoglio, R., Sciascia, S., Gattei, V. and Roccatello, D. 2022. Extrahepatic Manifestations of Chronic HBV Infection and the Role of Antiviral Therapy. J Clin Med. 11: 6247.

Mazzaro, C., Dal Maso, L., Mauro, E., Visentini, M., Tonizzo, M., Gattei, V., Andreone, P. and Pozzato, G. 2020. Hepatitis C virus- related cryoglobulinemic vasculitis: A review of the role of the new direct antiviral agents (DAAs) therapy. Autoimmun Rev. 19: 102589.

Pesavento, P. A., Jackson, K., Hampson, T. S. T. T. B., Munday, J. S., Barrs, V. R. and Beatty, J. A. 2019. A Novel Hepadnavirus is Associated with Chronic Hepatitis and Hepatocellular Carcinoma in Cats. Viruses. 11: 969.

Piewbang, C., Dankaona, W., Poonsin, P., Yostawonkul, J., Lacharoje, S., Sirivisoot, S., Kasantikul, T., Tummaruk, P. and Techangamsuwan, S. 2022. Domestic cat hepadnavirus associated with hepatopathy in cats: A retrospective study. J Vet Intern Med. 36: 1648–1659.

Piewbang, C., Wardhani, S. W., Chaiyasak, S., Yostawonkul, J., Chai-In, P., Boonrungsiman, S., Kasantikul, T. and Techangamsuwan, S. 2020. Insights into the genetic diversity, recombination, and systemic infections with evidence of intracellular maturation of hepadnavirus in cats. PLoS One. 15: e0241212.

Pramoolsinsap, C., Busagorn, N. and Kurathong, S. 1996. Haemostatic abnormalities in patients with liver disease associated with viral hepatitis. J Med Assoc Thai. 79: 681–688.

Scavone, D., Lauzi, S., Stranieri, A., Tramontano, G., Ratti, G. and Paltrinieri, S. 2022. Evaluating the presence of domestic cat hepadnavirus viraemia in cats with biochemical alterations suggestive of liver disease. Vet Rec. 191: e1626.

Shofa, M., Ohkawa, A., Okabayashi, T., Kaneko, Y. and Saito, A. 2023. Development of a direct duplex real-time PCR assay for rapid detection of domestic cat hepadnavirus. J Vet Diagn Invest. 35: 139–144.

Silva, B. B. I., Chen, J.-Y., Villanueva, B. H. A., Lu, Z.-Y., Hsing, H.-Z., Montecillo, A. D., Shofa, M., Minh, H., Chuang, J.-P., Huang, H.-Y., Saito, A. and Chuang, K.-P. 2023. Genetic Diversity of Domestic Cat Hepadnavirus in Southern Taiwan. Viruses. 15: 2128.

Song, Z., Lin, S., Wu, X., Ren, X., Wu, Y., Wen, H., Qian, B., Lin, H., Huang, Y., Zhao, C., Wang, N., Huang, Y., Peng, B., Li, X., Peng, H. and Shen, S. 2023. Hepatitis B virus-related intrahepatic cholangiocarcinoma originates from hepatocytes. Hepatol Int. 17: 1300–1317.

Stone, C., Petch, R., Gagne, R. B., Nehring, M., Tu, T., Beatty, J. A. and VandeWoude, S. 2022. Prevalence and Genomic Sequence Analysis of Domestic Cat Hepadnavirus in the United States. Viruses. 14: 2091.

Summers, J., Smolec, J. M. and Snyder, R. 1978. A virus similar to human hepatitis B virus associated with hepatitis and hepatoma in woodchucks. Proc Natl Acad Sci U S A. 75: 4533–4537.

Takahashi, K., Kaneko, Y., Shibanai, A., Yamamoto, S., Katagiri, A., Osuga, T., Inoue, Y., Kuroda, K., Tanabe, M., Okabayashi, T., Naganobu, K., Minobe, I. and Saito, A. 2022. Identification of domestic cat hepadnavirus from a cat blood sample in Japan. J Vet Med Sci. 84: 648–652.

Tessmann, A., Sumienski, J., Sita, A., Mallmann, L., Birlem, G. E., da Silva Nunes, N. J., Lupion, C. G., Eckert, J. S., Demoliner, M., Gularte, J. S., de Almeida, P. R., Spilki, F. R. and Weber, M. N. 2025. Domestic cat hepadnavirus genotype B is present in Southern Brazil. Virus Genes. 61: 81–86.

Wang, C., Wang, M., Cheng, P., Huang, H., Dong, W., Zhang, W.-W., Li, P.-P., Lin, C., Pan, Z.-Y., Wu, M.-C. and Zhou, W.-P. 2017. Hepatitis B virus X protein promotes the stem-like properties of OV6+ cancer cells in hepatocellular carcinoma. Cell Death Dis. 8: e2560.

Wardhani, S. W., Lacharoje, S., Kasantikul, T., Piewbang, C. and Techangamsuwan, S. 2025. Longitudinal observation of chronic domestic cat hepadnavirus infection in cats with evidence of extrahepatic involvement. J Feline Med Surg. 27: 1098612X251359148.

Wardhani, S. W., Tummaruk, P., Piewbang, C. and Techangamsuwan, S. 2023. Quantification of domestic cat hepadnavirus DNA in various body fluid specimens of cats: the potential viral shedding routes. Front Vet Sci. 10: 1248445.