Natural co‐infection of divergent hepatitis B and C virus homologues in carnivores

Abstract

In humans, co‐infection of hepatitis B and C viruses (HBV, HCV) is common and aggravates disease outcome. Infection‐mediated disease aggravation is poorly understood, partly due to lack of suitable animal models. Carnivores are understudied for hepatitis virus homologues. We investigated Mexican carnivores (ringtails, Bassariscus astutus) for HBV and HCV homologues. Three out of eight animals were infected with a divergent HBV termed ringtail HBV (RtHBV) at high viral loads of 5 × 109 –1.4 × 1010 copies/ml serum. Two of the RtHBV‐infected animals were co‐infected with a divergent hepacivirus termed ringtail hepacivirus (RtHV) at 4 × 106–7.5 × 107 copies/ml in strain‐specific qRT‐PCR assays. Immunofluorescence assays relying on HBV core and RtHV NS3/4a proteins indicated that none of the animals had detectable hepadnavirus core‐specific antibodies, whereas one RtHV‐infected animal had concomitant RtHV‐specific antibodies at 1:800 end‐point titre. RtHBV and RtHV complete genomes showed typical HBV and HCV structure and length. All RtHBV genomes were identical, whereas RtHV genomes showed four amino acid substitutions located predominantly in the E1/E2‐encoding genomic regions. Both RtHBV (>28% genomic nucleotide sequence distance) and RtHV (>30% partial NS3/NS5B amino acid sequence distance) formed new species within their virus families. Evolutionary analyses showed that RtHBV grouped with HBV homologues from different laurasiatherian hosts (carnivores, bats, and ungulates), whereas RtHV grouped predominantly with rodent‐borne viruses. Ancestral state reconstructions showed that RtHV, but not RtHBV, likely emerged via a non‐recent host switch involving rodent‐borne hepacivirus ancestors. Conserved hepatitis virus infection patterns in naturally infected ringtails indicate that carnivores may be promising animal models to understand HBV/HCV co‐infection.

Transcriptome mining extends the host range of the Flaviviridae to non-bilaterians

“…Similarly, ancestral state reconstructions have previously shown that cross-species transmission from rodents is likely the source of the sloth and ringtail hepaciviruses ( Moreira-Soto et al. 2020 ; Jo et al. 2022 ).…”

Transcriptome mining extends the host range of theFlaviviridaeto non-bilaterians

“…The clear relatedness between GmebHV and rodent hepacivirus (QLM02863), combined with evidence from our co-evolutionary analyses, suggests that this sequence might represent a cross-species transmission event between bats and rodents. Similarly, ancestral state reconstructions have previously shown that cross-species transmission from rodents is likely the source of the sloth and ringtail hepaciviruses (Jo et al 2022;Moreira-Soto et al 2020).…”

Metagenomics-Based Discovery of New Hepadnaviruses

“…Next-generation sequencing (NGS) analyses can be utilized to discover viral sequences in hosts, especially in cases of novel viruses with no reference sequences. With advances in NGS technology in recent years, new hepadnaviruses have been successively discovered in numerous animal species (metagenomic HBV), such as fish [4,7,8], frogs [6,9,10], bats [5,11], cats [12], dogs [13], antelope [14], raccoons [15], horses [16], and shrews [17][18][19]. These findings have yielded a deeper understanding of the origin and evolution of hepadnaviruses [20] together with studies on ancient HBV [21,22] and endogenous HBV in birds [23,24].…”