Genome and cell entry
Hepadnaviruses possess a unique genetic apparatus that radically distinguishes them from other families. Their genome is represented by a circular double-stranded DNA molecule, but it has a characteristic structural feature: one of the strands is incomplete and contains a physical nick.
When the virion (using hepatitis B virus as an example) enters a susceptible cell, its core initially ends up in the cytoplasm. To initiate the infectious process, the viral genome must be purposefully transported into the cell nucleus, where the first stages of reproduction unfold.
Nuclear phase: repair and transcription
Once inside the nucleus, the viral DNA undergoes an obligatory repair phase. The incomplete "plus-strand" is completed by cellular machinery, resulting in the formation of a stable, fully covalently closed circular DNA (cccDNA).
This repaired molecule serves as an ideal template. Cellular DNA-dependent RNA polymerase initiates transcription, creating two critically important types of viral RNA:
- Messenger RNA (mRNA): required for the subsequent synthesis of all viral proteins.
- Pregenomic RNA: functions as a full-length template for future viral genome replication.
Cytoplasmic phase: translation and assembly
The synthesized viral RNAs leave the nucleus and move back into the cytoplasm. Here, translation is initiated based on the mRNA. The cell actively produces viral components: capsid proteins, viral polymerase, and surface antigens.
Concurrently with protein synthesis, new nucleocapsids are assembled. The core proteins of the virus densely cluster around the pregenomic RNA molecule and newly synthesized viral polymerase molecules. This prepares the platform for the final stage of genome maturation.
Reverse transcription and exocytosis
The main feature of hepadnaviruses is that the synthesis of new DNA occurs inside the forming capsid. Viral RNA-dependent DNA polymerase (reverse transcriptase) uses the pregenomic RNA as a template.
The process proceeds in a strict sequence:
- First, a complete DNA "minus-strand" is synthesized on the pregenomic template.
- Then, based on the completed "minus-strand", the "plus-strand" is built, remaining incomplete and replicating the initial structure of the viral genome.
After the nucleocapsid is formed, it is transported to the membranes of the endoplasmic reticulum (ER) or Golgi apparatus. There, interacting with regions containing the surface antigen (HBsAg), the virion acquires a supercapsid (envelope). Fully formed viral particles leave the host cell via exocytosis.
Briefly: answers to topical questions
Which structural proteins are synthesized during the cytoplasmic stage of reproduction?
During the cytoplasmic stage of hepadnavirus reproduction, capsid proteins and surface antigens are synthesized. After viral RNAs move into the cytoplasm, translation of the following proteins begins:
- Capsid proteins — form the core of the virus, assembling around the pregenomic RNA and viral polymerase to form the nucleocapsid.
- Surface antigens (HBsAg) — structural components required for the subsequent formation of the supercapsid.
In addition to structural elements, a non-structural enzyme—viral polymerase, which drives reverse transcription—is also translated at this stage.
Which cellular organelles are involved in the assembly and release of the hepatitis B virus?
The membranes of the endoplasmic reticulum and Golgi apparatus are involved in the assembly and release of the hepatitis B virus. The process of virion formation and release includes the following structures:
- Endoplasmic reticulum (ER) — provides membranes containing the HBsAg surface antigen, on which the nucleocapsid acquires its supercapsid.
- Golgi apparatus — its membranes also serve as the site of formation for the outer lipoprotein envelope of the virus.
Following the completion of assembly on the membranes of these organelles, the exit of formed virions from the cell occurs via exocytosis.
To memorize the phase sequence, use the acronym NCRE: Nucleus (repair and transcription) → Cytoplasm (protein synthesis) → Reverse transcription (inside the capsid) → Exit (via ER/Golgi).
Class and exam questions
Why does the hepatitis B virus need RNA if its genome consists of DNA?
During reproduction, the virus forms pregenomic RNA. It serves as a template on which viral reverse transcriptase synthesizes new viral DNA molecules inside the assembling capsid.
Where exactly does the completion of the incomplete viral DNA strand take place?
This process is carried out strictly in the nucleus of the infected cell. As a result of repair, a fully functional covalently closed circular DNA is formed.
Where and how do new virions acquire their outer envelope?
The nucleocapsid acquires a supercapsid on the membranes of the endoplasmic reticulum or Golgi apparatus, which contain the viral surface antigen (HBsAg).
What else to study on this topic
- Mechanism of formation and functions of covalently closed circular DNA (cccDNA)
- Features of viral RNA-dependent DNA polymerase activity
- The process of supercapsid assembly on ER and Golgi membranes
- Functional differences between mRNA and pregenomic RNA in the hepadnavirus cycle
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