The first full-length endogenous hepadnaviruses: identification and analysis

Abstract

In silico screening of metazoan genome data identified multiple endogenous hepadnaviral elements in the budgerigar (Melopsittacus undulatus) genome, most notably two elements comprising about 1.3 × and 1.0 × the full-length genome. Phylogenetic and molecular dating analyses show that endogenous budgerigar hepatitis B viruses (eBHBV) share an ancestor with extant avihepadnaviruses and infiltrated the budgerigar genome millions of years ago. Identification of full-length genomes with preserved key features like ε signals could enable resurrection of ancient BHBV.

Fig 1

Endogenous full-length hepadnavirus genomes identified in budgerigar. (A) Endogenous budgerigar hepadnavirus eBHBV1 (1.3×) and eBHBV2 (1.0×) sequences are depicted using 1.0× parrot HBV genome as a reference (top). (B) Phylogenetic relationships between exogenous and endogenous hepadnaviruses. eBHBV1 and eBHBV2 sequences are highlighted in red. Bootstrap values greater than 70 percentage points are shown.

Fig 2

Endogenous budgerigar hepadnavirus features related to viral replication. (A) Alignment of endogenous and exogenous hepadnavirus polymerase TP domain amino acid sequences. The conserved tyrosine residue used for priming is marked by asterisk. (B) Comparison of ε secondary structure as well as DR1 sequences of eBHBV and representative exogenous hepadnaviruses of human (HBV), duck (DHBV), and heron (HHBV) (1). Template sites for initial priming of minus DNA synthesis and primers attached to tyrosine on TP are depicted. Red arrows indicate direction of minus DNA elongation post-primer translocation.