Hepatitis B virus large surface protein (L-HBsAg)

The Hepatitis B virus large surface protein (L-HBsAg) is a critical structural component of the viral envelope, composed of the pre-S1, pre-S2, and S domains [6, 10, 12]. It is primarily responsible for mediating viral entry into human hepatocytes by binding to the sodium taurocholate cotransporting polypeptide (NTCP) receptor through its N-terminal pre-S1 domain [1, 3, 8, 20]. In addition to its role in infection, L-HBsAg is essential for the assembly and budding of infectious virions and the production of subviral particles that contribute to immune evasion by acting as decoys [6, 7, 11]. Chronic accumulation of L-HBsAg, particularly variants with pre-S mutations, induces significant endoplasmic reticulum (ER) stress and is strongly associated with the progression of liver disease to cirrhosis and hepatocellular carcinoma (HCC) [6, 20, 22]. Therapeutically, L-HBsAg is targeted by entry inhibitors such as bulevirtide, which blocks the NTCP receptor, and by neutralizing monoclonal antibodies that prevent viral attachment [1, 2, 4, 9]. Monitoring serum levels of L-HBsAg and its pre-S domains serves as a key biomarker for assessing viral activity and the risk of oncogenic transformation in patients with chronic hepatitis B [11, 21].

Other names

LHBsLarge envelope proteinL glycoproteinLarge S proteinMajor surface antigenpre-S1/pre-S2/S proteinHBV-LP

Viral entry inhibition by blocking the interaction between the pre-S1 domain and the host NTCP receptor; viral neutralization by antibodies binding to envelope epitopes.