Hepatitis B Virus: Structure, Entry, Replication, and Immune Evasion

Hepatitis B virus (HBV) is a global health concern, affecting millions and leading to severe liver diseases like cirrhosis and hepatocellular carcinoma. Understanding its biological mechanisms is essential for developing effective treatments and preventive measures.

Hepatitis B Virus Structure

The Hepatitis B virus (HBV) is a small, enveloped DNA virus in the Hepadnaviridae family. Its structure features a nucleocapsid, a protein shell encasing the viral DNA and DNA polymerase enzyme. This nucleocapsid, composed of core proteins, is vital for the virus’s replication and assembly.

Surrounding the nucleocapsid is the viral envelope, a lipid bilayer from the host cell membrane. Embedded within this envelope are surface antigens, primarily the hepatitis B surface antigen (HBsAg), which facilitate the virus’s attachment to host cells. These antigens are also targets for the immune system and are used in diagnostic tests.

The viral genome is a partially double-stranded circular DNA, encoding four overlapping open reading frames responsible for producing proteins necessary for the virus’s life cycle. The compact genome allows efficient use of genetic material, enabling the virus to maintain its small size while encoding all necessary functions.

Host Cell Entry

The entry of Hepatitis B virus (HBV) into host cells is a carefully orchestrated process. The virus targets hepatocytes, or liver cells, using surface proteins to attach to specific receptors on the hepatocyte membrane. This specificity is primarily mediated by the host receptor sodium taurocholate co-transporting polypeptide (NTCP).

Upon attachment, the virus undergoes conformational changes, allowing it to penetrate the host cell membrane. This involves a mechanism where the viral envelope fuses with the host cell membrane, facilitated by host factors and viral proteins. Once the viral core is released into the cytoplasm, it moves towards the nucleus for replication and transcription.

Viral Replication

Once inside the hepatocyte, HBV’s replication process begins in the nucleus. The partially double-stranded viral DNA genome is converted into covalently closed circular DNA (cccDNA), a stable form that serves as a template for transcription. This cccDNA is a persistent reservoir, contributing to chronic infection. The transcription of cccDNA generates several RNA species, including pregenomic RNA (pgRNA), crucial for viral replication.

The pgRNA is transported to the cytoplasm, serving as a template for reverse transcription, catalyzed by the viral DNA polymerase. This enzyme converts pgRNA into new viral DNA, a hallmark of HBV replication. The newly synthesized DNA forms the core of nascent nucleocapsids, which can either be enveloped and secreted as new virions or recycled back to the nucleus to replenish the cccDNA pool.

Immune Evasion Strategies

The Hepatitis B virus (HBV) employs various tactics to evade the host immune response. One strategy involves producing large quantities of subviral particles composed solely of surface antigens. These decoy particles outnumber actual virions, distracting the immune system and preventing an effective neutralizing antibody response.

HBV also modulates the host’s immune signaling pathways. By interfering with key immune molecules like cytokines and chemokines, the virus dampens the inflammatory response. This modulation is achieved through the interaction of viral proteins with host cellular machinery, altering the expression and activity of these immune mediators. Additionally, HBV can influence the antigen-presenting capabilities of infected cells, impairing the activation of T cells essential for a robust immune attack.