HBV structure and replication

HBV Structure - The Dane Particle

• Dane Particle: The complete, infectious virion of HBV; 42 nm in diameter.
• Envelope:
  • Outer lipid layer containing Hepatitis B surface antigen (HBsAg).
  • HBsAg is the basis for the HBV vaccine and is detectable in serum during infection.
• Core (Nucleocapsid):
  • Icosahedral core composed of Hepatitis B core antigen (HBcAg).
  • Contains Hepatitis B e-antigen (HBeAg), a marker of active replication and high infectivity.
• Genome & Polymerase:
  • Circular, partially double-stranded DNA genome.
  • Carries its own DNA polymerase with reverse transcriptase activity.

⭐ Non-infectious HBsAg spheres and filaments are present in patient serum at concentrations much higher than infectious Dane particles.

HBV Replication - Reverse Transcriptase Twist

• Entry & Nuclear Translocation: Virion enters hepatocyte, uncoats, and the partially double-stranded DNA (pdsDNA) genome travels to the nucleus.
• cccDNA Formation: Inside the nucleus, host DNA polymerase repairs the pdsDNA into a stable covalently closed circular DNA (cccDNA). This cccDNA serves as a persistent template for all viral transcripts.
• Transcription: Host RNA polymerase transcribes cccDNA into viral mRNAs and a +ssRNA pre-genome.
• Core Assembly & Reverse Transcription: In the cytoplasm, the +ssRNA pre-genome is packaged into a new core particle along with the viral polymerase, which has reverse transcriptase (RT) activity.
  • The RT synthesizes a -ssDNA strand from the RNA template.
  • The original RNA template is degraded.
  • A new +ssDNA strand is synthesized, but incompletely, creating the final partially dsDNA genome.
• Release: New virions are assembled and released from the hepatocyte.

⭐ HBV is a DNA virus that uniquely replicates via an RNA intermediate using reverse transcriptase. This RT is the primary target for antiviral nucleoside/nucleotide analogs (NRTIs) like Tenofovir and Entecavir.

HBV Serology - Decoding the Blood

• HBsAg (Surface Antigen): First marker to appear. Indicates active infection (acute or chronic).
• HBsAb / anti-HBs (Surface Antibody): Indicates immunity from vaccination or recovery from prior infection.
• HBcAb / anti-HBc (Core Antibody):
  • IgM: Marker of acute infection; positive during the "window period".
  • IgG: Marker of past or chronic infection.
• HBeAg (Envelope Antigen): Indicates high infectivity and active viral replication.
• HBeAb / anti-HBe (Envelope Antibody): Indicates low infectivity and ↓ replication.

⭐ Window Period: Time when both HBsAg and HBsAb are negative. Diagnosis is made by detecting IgM anti-HBc.

• HBV is an enveloped, partially double-stranded circular DNA virus, unique for replicating via an RNA intermediate using its own reverse transcriptase.
• The infectious virion is known as the Dane particle.
• Replication occurs in the nucleus and cytoplasm; host RNA polymerase creates an RNA template, which is then converted back to DNA by viral reverse transcriptase.
• HBsAg on the surface indicates infection, while HBeAg correlates with high infectivity and active viral replication.