Replication strategy of human hepatitis B virus

Abstract

To study the replication strategy of the human hepatitis B virus, the 5' end of the RNA pregenome and the initiation sites of DNA plus and minus strands have been mapped. The RNA pregenome was found to be terminally redundant by 120 nucleotides; it is initiated within the pre-C region and may also function as mRNA for synthesis of the major core protein and the hepatitis B virus reverse transcriptase. The hepatitis B virus DNA minus strand is initiated within the direct repeat sequence DR1, it contains a terminal redundancy of up to eight nucleotides, and its synthesis does not require any template switch. The DNA plus strand is primed by a short oligoribonucleotide probably derived from the 5' end of the RNA pregenome, and its synthesis is initiated close to the direct repeat sequence DR2. For its elongation to pass the discontinuity in the DNA minus strand an intramolecular template switch occurs using the terminal redundancy of this template. Thus, the route of reverse transcription and DNA replication of hepatitis B viruses is fundamentally different from that of retroviruses.

Incidence and clinical significance of hepatitis B virus precore gene translation initiation mutations in e antigen‐negative patients

“…A selection mechanism requiring neither an immunological nor a functional role for precore products may operate during HBV nucleocapsid assembly. Precore mRNA transcripts harbouring translation initiation mutations may escape discrimination that operates via the translational inactivation of transcripts initiating at the precore start codon [27][28][29] and may therefore be packaged more efficiently.…”

Compact organization of the hepatitis B virus genome

“…These ORFs represent the gene sequences that encode the virus nucleocapsid (core) and envelope (surface) proteins as well as the virus replicase (polymerase) and a protein that appears to be involved in virus gene expression (X). Three major, unspliced messenger RNA (mRNA) transcripts are synthesized by a cell-derived RNA polymerase I1 (17). The longest, a 3.5-kilobase (kb) terminally redundant transcript, is used both as a template for genome replication by reverse transcription and as the mRNA for expression of the core and polymerase proteins.…”

“…The most highly conserved nucleotide sequence of the HBV genome spans the pre-core and core ORFs. Termed the U5-like region for its homology to the 5'-unique region of retrovirus long terminal repeats (20,21), this region has been found to reside in the terminal repeats of the linear HBV RNA pre-genome (17). Within a 62nucleotide domain 54, or 87%, of the nucleotides are identical at a given position among 16 mammalian hepadnavirus genomes (Fig.…”

Structure and function of the encapsidation signal of hepadnaviridae

“…It contains a number of inverted repeat sequences, which have the potential to form secondary, and possibly tertiary, structures that could be recognized in the packaging reaction [5]. Although both genomic transcripts of HBV contain ε near the 5′ end, only the shorter, viz, pgRNA, is encapsidated [5,[10][11][12] and reverse transcribed [13]. Nassal and co-workers [14] showed that translating 80S ribosomes advancing into ε prevent it from functioning and concluded that the ability of ε to be trans-lated is decisive in determining whether or not an εcontaining RNA is packaged.…”