A Novel Hepadnavirus Identified in an Immunocompromised Domestic Cat in Australia

Abstract

High-throughput transcriptome sequencing allows for the unbiased detection of viruses in host tissues. The application of this technique to immunosuppressed animals facilitates the detection of viruses that might otherwise be excluded or contained in immunocompetent individuals. To identify potential viral pathogens infecting domestic cats we performed high-throughput transcriptome sequencing of tissues from cats infected with feline immunodeficiency virus (FIV). A novel member of the Hepadnaviridae, tentatively named domestic cat hepadnavirus, was discovered in a lymphoma sample and its complete 3187 bp genome characterized. Phylogenetic analysis placed the domestic cat hepadnavirus as a divergent member of mammalian orthohepadnaviruses that exhibits no close relationship to any other virus. DNA extracted from whole blood from pet cats was positive for the novel hepadnavirus by PCR in 6 of 60 (10%) FIV-infected cats and 2 of 63 (3.2%) FIV-uninfected cats. The higher prevalence of hepadnavirus viraemia detected in FIV-infected cats mirrors that seen in human immunodeficiency virus-infected humans coinfected with hepatitis B virus. In summary, we report the first hepadnavirus infection in a carnivore and the first in a companion animal. The natural history, epidemiology and pathogenic potential of domestic cat hepadnavirus merits additional investigation.

Keywords: Orthohepadnavirus; carnivore; domestic cat; feline; hepadnavirus; hepatitis B; immuosuppression; pathogen discovery; virus.

Figure 1

Genome organization of the domestic cat hepadnavirus. The complete genome consists of 3187 bp. The innermost circles represent the GC (blue) and AT (green) content of the genome. The proteins encoded by the polymerase, surface, core and X ORFs are labelled, as are the positions of primers used in this study (Table 1).

Figure 2

The Phylogenetic position of domestic cat hepadnavirus within the Hepadnaviridae. (A) Maximum likelihood phylogeny based on the P (polymerase) ORF and incorporating a wide range of vertebrate hepadnaviruses, including Roundleaf bat HBV (YP_009045991), Horseshoe bat HBV (YP_009045995), Long-fingered bat HBV (YP_007677999), Tent-making bat HBV (YP_009045999), Bat HBVs (AVW79974, ARM20233, ARM20221, and AQT40960), Ground squirrel hepatitis virus (NP_040994), Arctic ground squirrel HBV (AAB08032), Woodchuck hepatitis virus (NP_671813); Hepatitis B virus (YP_009173866), Woolly monkey HBV (YP_009175034), Capuchin monkey HBV (AVV68831), Bluegill hepadnavirus (YP_009259541), Astatotilapia metahepadnavirus (ref7), Tetra hepadnavirus (ref7), Icefish hepadnavirus (ref7), Heron HBV (NP_040998), Parrot HBVs (YP_004956864, AFY97702), Ross's goose HBV (YP_024968), Duck HBV (NP_039821), Snow goose HBV (YP_031695), Stork HBV (CAC80811), Sheldgoose HBV (YP_024974), Tinamou HBV (YP_009389524), Tibetan frog hepadnavirus (YP_009259545), White sucker HBV (YP_009165599). This tree was mid-point rooted for clarity only. Phylogenies based on the (B) C ORF (C) and S ORF of mammalian orthohepadnaviruses and rooted by the homologous sequences found in the bluegill. In all phylogenies the host groups of each virus species are indicated by symbols to the right of the tree and branch lengths are scaled according to the number of amino acid substitutions per site. SH-like support values >0.80 for nodal support are shown by asterisks in all cases.