Hepatitis B virus preS domain of envelope protein (preS)

The **preS domain** of the hepatitis B virus (HBV) envelope protein is a composite region comprising two contiguous segments—preS1 (N-terminal) and preS2 (central)—which, together with the S (small) domain, form the large (L) envelope protein of HBV[1][2][9]. These domains are *essential for viral infectivity*, as the N-terminal residues of preS1 (approximately the first 48 amino acids) mediate **binding to the viral receptor sodium taurocholate co-transporting polypeptide (NTCP)** on hepatocytes, initiating infection[1][2][9]. The preS region also participates in virus assembly, notably at the preS1/preS2 junction, where interactions with the viral capsid occur during particle formation[1][3]. Myristoylation at the N-terminus of preS1 is crucial for receptor interaction and membrane insertion during infection[2]. In addition, the preS domain is a principal target for neutralizing antibodies and entry inhibitors—such as bulevirtide—which block HBV entry by mimicking the NTCP-binding function of preS1[2]. Mutagenesis of the preS domains affects infectivity, morphogenesis, and immune recognition, implicating this region in disease progression, immune evasion, and antiviral resistance[1][2][5]. Chronic infection by HBV facilitated by preS-mediated attachment can lead to serious liver diseases, including hepatic inflammation and hepatocellular carcinoma[4]. **Key points:** - The preS domain is not a human gene product, but a viral protein domain vital for HBV life cycle and pathogenesis. - Its functions span **host cell receptor binding, membrane fusion, virion assembly, and immune evasion**. - It is the molecular target for entry inhibitors, notably **bulevirtide**, used clinically for hepatitis B and D treatment. - Variants or mutations in preS are relevant for vaccine design, drug resistance, and disease monitoring[2][5].

Other names

preS domainpreS1 domainpreS2 domainLarge envelope protein domainL protein preS

Inhibition of viral entry via blocking preS1-NTCP interaction