Hepadnaviridae (taxid:10404)

VIRION

Enveloped, spherical. Diameter from about 42nm. Icosahedric capsid with a T=4 symmetry.

GENOME

Partially dsDNA circular genome, about 3.2 kb in size. Encodes for 7 proteins.
On rare non-specific recombination, the viral genome can be integrated in host chromosome. This inactivates the integrated virus but can gives the host cell a replicative advantage sometimes leading to hepatocarcinoma.

GENE EXPRESSION

The minichromosome is transcribed by cellular RNA polymerase II under the control of three to four promoters (the core, pre-S1, pre-S2/S promoters, and the X promoter in mammalian viruses) and two enhancer regions (ENH1 and ENH2). The pre-genomic RNA is alternatively spliced. The unspliced form is exported from the nucleus through a PRE motif possibly by capsid protein. The Polymerase and short S proteins are expressed by leaky scanning from the pg mRNA and the S mRNA respectively.

ENZYMES

• Reverse transcriptase
  • RNA-dependent DNA polymerase [P]
  • DNA-dependent DNA polymerase [P]
  • Protein-primed terminal transferase [P]
• RNAse H [P]

REPLICATION

CYTOPLASMIC/NUCLEAR

1. Virus attaches to host receptors through major surface antigen and enters the cell by an unknown mechanism.
2. Relaxed circular DNA (RC-DNA) and capsid are transported via microtubules to the nucleus where DNA is released through the nuclear pore, and repaired to form covalently closed circular DNA (cccDNA).
3. Transcription by RNA polymerase II of the pregenomic RNA (pgRNA) and subgenomic mRNAs, inducing synthesis of all the viral proteins.
4. pgRNA is encapsidated, together with the P protein, and reverse-transcribed inside the nucleocapsid in (-)DNA covalently linked to P protein.
5. (+)DNA synthesis from the (-)DNA template generates new RC-DNA.
6. Transport to the nucleus of new RC-DNA leads to cccDNA amplification; alternatively, the RC-DNA containing nucleocapsids are enveloped at the ER, and new virions are released by exocytosis.

Host-virus interaction

Primary receptor

HBV L surface protein can bind to heparan sulfate

Entry receptor

HBV L surface protein Binds to SLC10A1/NTCP in order to enter hepatocytes.

Autophagy modulation

HBV protein HBx seems to be able to increase autophagy through the up-regulation of host beclin 1 expression .

Cell-cycle modulation

HBV protein HBx protein deregulates cell cycle checkpoint controls at G0/G1 and G2/M .

Innate immune response inhibition

HBV protein HBx directly interacts with and inhibits host MAVS protein by inducing its ubiquitination and targeting it for degradation .