Conservation of the HBV RNA element epsilon in nackednaviruses reveals ancient origin of protein-primed reverse transcription.
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AbstractHepadnaviruses, with the human hepatitis B virus as prototype, are small, enveloped hepatotropic DNA viruses which replicate by reverse transcription of an RNA intermediate. Replication is initiated by a unique protein-priming mechanism whereby a hydroxy amino acid side chain of the terminal protein (TP) domain of the viral polymerase (P) is extended into a short DNA oligonucleotide, which subsequently serves as primer for first-strand synthesis. A key component in the priming of reverse transcription is the viral RNA element epsilon, which contains the replication origin and serves as a template for DNA primer synthesis. Here, we show that recently discovered non-enveloped fish viruses, termed nackednaviruses [C. Lauber et al., Cell Host Microbe 22, 387-399 (2017)], employ a fundamentally similar replication mechanism despite their huge phylogenetic distance and major differences in genome organization and viral lifestyle. In vitro cross-priming studies revealed that few strategic nucleotide substitutions in epsilon enable site-specific protein priming by heterologous P proteins, demonstrating that epsilon is functionally conserved since the two virus families diverged more than 400 Mya. In addition, other cis elements crucial for the hepadnavirus-typical replication of pregenomic RNA into relaxed circular double-stranded DNA were identified at conserved positions in the nackednavirus genomes. Hence, the replication mode of both hepadnaviruses and nackednaviruses was already established in their Paleozoic common ancestor, making it a truly ancient and evolutionary robust principle of genome replication that is more widespread than previously thought.
CitationProc Natl Acad Sci U S A. 2021 Mar 30;118(13):e2022373118. doi: 10.1073/pnas.2022373118.
AffiliationTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
PublisherAcademy of Sciences
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- Creative Commons
- Mapping of Functional Subdomains in the Terminal Protein Domain of Hepatitis B Virus Polymerase.
- Authors: Clark DN, Flanagan JM, Hu J
- Issue date: 2017 Feb 1
- A pregenomic RNA sequence adjacent to DR1 and complementary to epsilon influences hepatitis B virus replication efficiency.
- Authors: Tang H, McLachlan A
- Issue date: 2002 Nov 10
- Few basepairing-independent motifs in the apical half of the avian HBV ε RNA stem-loop determine site-specific initiation of protein-priming.
- Authors: Gajer M, Dörnbrack K, Rösler C, Schmid B, Beck J, Nassal M
- Issue date: 2017 Aug 2
- A bulged region of the hepatitis B virus RNA encapsidation signal contains the replication origin for discontinuous first-strand DNA synthesis.
- Authors: Nassal M, Rieger A
- Issue date: 1996 May
- Generation of replication-competent hepatitis B virus nucleocapsids in insect cells.
- Authors: Seifer M, Hamatake R, Bifano M, Standring DN
- Issue date: 1998 Apr