Domestic Cat Hepadnavirus: Molecular Epidemiology and Phylogeny in Cats in Hong Kong

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 × 103 copies/mL of whole blood (range for the 5th to the 95th percentile, 3.33 × 103 to 2.2 × 105 copies per mL). Two outliers had higher viral loads of 1.88 × 107 copies/mL and 4.90 × 109 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.

Genetic diversity of domestic cat hepadnavirus in Taiwan

“…Our phylogenetic analysis using the maximum likelihood method on all available complete sequences of DCH, and genomes of other members of the Orthohepadnavirus, Metahepadnavirus, Herpetohepadnavirus, and Avihepadvirus genera supports previous Generally, DCH/NPUST-006/TWN/2023 belongs to clade A1, proposed previously by other authors [12], while the rest of the Taiwan strains belong to clade A2 under genotype A. However, with the addition of more sequences particularly those from Türkiye and Taiwan strains, our phylogenetic analysis of the currently available DCH sequences, implemented by constructing a maximum likelihood tree using TIM+F+I+R2 as the best fit and chosen model according to the Bayesian information criterion, did not reveal robust branching support for a clear distinction between the proposed clades A1 and A2 (Figure 3).…”

“…Phylogenetic relationships among the Taiwan strains, particularly the divergence of DCH/NPUST-006 from the other strains as observed in Figure 3, are strongly supported by the phylogenetic trees based on sequences of core, polymerase, surface, and X proteins (Figure 4). Maximum-likelihood trees of both the polymerase and surface proteins (Figures 4a and 4b) generally show the two subdivisions of Genotype A as proposed previously by other authors [12]. However, similar to that of the whole genome sequence tree, there is no robust bootstrap support for this proposed subdivision.…”

“…Maximum-likelihood trees of both the polymerase and surface proteins (Figures 4a and 4b) generally show the two subdivisions of Genotype A as proposed previously by other authors [12]. However, similar to that of the whole genome sequence tree, there is no robust bootstrap support for this proposed subdivision.…”

The detection and full genomic characterization of domestic catOrthohepadnavirusesfrom Türkiye

“…Our phylogenetic analysis results showed that all positive samples obtained from domestic cats from Türkiye localized into Orthohepadnavirus genus. These findings raise the question of whether DCH can affect other domestic (Capozza, Decaro et al, 2021;Capozza et al, 2023;Choi et al, 2022;Diakoudi et al, 2022) or wild carnivores. We believe that future studies investigating hepadnaviruses in different carnivorous species are needed to understand the origin of DCH and its relationship with other species.…”

Conserved use of the sodium/bile acid cotransporter (NTCP) as an entry receptor by hepatitis B virus and domestic cat hepadnavirus

“…In 2018, an HBV-like virus, domestic cat hepadnavirus (DCH), was identified in domestic cats in Australia and was associated with feline chronic hepatitis (Aghazadeh et al, 2018), suggesting a similarity with HBV pathogenesis. Subsequently, DCH was identified in other countries, including Italy (Lanave et al, 2019), Thailand (Piewbang et al, 2020), Malaysia (Anpuanandam et al, 2021), United Kingdom (Jeanes et al, 2022), United States (Stone et al, 2022), Hong Kong (Capozza et al, 2023), and Japan (Takahashi et al, 2022). DCH has a partially double-stranded, circular DNA genome of ~3,200 bases in length (Aghazadeh et al, 2018).…”