Hepatitis B virus morphogenesis

Abstract

The hepatitis B virus (HBV) particle consists of an envelope containing three related surface proteins and probably lipid and an icosahedral nucleocapsid of approximately 30 nm diameter enclosing the viral DNA genome and DNA polymerase. The capsid is formed in the cytosol of the infected cell during packaging of an RNA pregenome replication complex by multiple copies of a 21-kDa C protein. The capsid gains the ability to bud during synthesis of the viral DNA genome by reverse transcription of the pregenome in the lumen of the particle. The three envelope proteins S, M, and L shape a complex transmembrane fold at the endoplasmic reticulum, and form disulfide-linked homoand heterodimers. The transmembrane topology of a fraction of the large envelope protein L changes posttranslationally, therefore, the N terminal domain of L (preS) finally appears on both sides of the membrane. During budding at an intracellular membrane, a short linear domain in the cytosolic preS region interacts with binding sites on the capsid surface. The virions are subsequently secreted into the blood. In addition, the surface proteins can bud in the absence of capsids and form subviral lipoprotein particles of 20 nm diameter which are also secreted.

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada

“…Positive-sense strand synthesis by viral polymerase and pregenomic mRNA degradation by a ribonuclease follows. The encapsidated viral genome may now be enveloped by a lipid envelope containing embedded HBsAg and be secreted from the host hepatocyte [47][48][49].…”

Involvement of host cellular multivesicular body functions in hepatitis B virus budding

“…Approximately 15-40% of HBV carriers develop cirrhosis, liver failure, and/or hepatocellular carcinoma (1), making HBV one of the most important human tumor viruses. Infectious HBV virions, also called Dane particles, are double-shelled, 42-nm spheres containing a 3.2-kb, relaxed circular ds viral DNA inside an inner icosahedral nucleocapsid and an outer shell containing three viral envelope proteins (S, M, and L) and presumably lipid (2)(3)(4). In the nuclei of infected cells, HBV virion DNA is converted into covalently closed circular viral DNA and transcribed to produce a terminally redundant pregenomic RNA (pgRNA).…”

“…HBV core protein encapsidates this pgRNA together with the viral DNA polymerase into nucleocapsids (NCs), within which pgRNA is reverse transcribed into dsDNA (5). Mature, DNA-containing NCs can then be enveloped by the viral surface proteins, yielding progeny virions (3).…”

“…Among other factors complicating study of these processes, HBV-infected cells or cells transfected with HBV genomic DNA produce, in addition to virions, a dramatic excess of subviral particles (SVPs), which are 20-nm diameter spherical and filamentous particles consisting only of lipid and HBV envelope proteins, predominantly S (3,4,6). SVPs can reach levels 10,000-fold higher than infectious virions in the serum of HBV carriers, where they may act as immunological decoys.…”

“…In the absence of more direct information, it is generally presumed that HBV virions bud into the same compartment and exit the cell by the same secretory pathway (3). However, the extent to which virion production parallels or is distinct from SVP production remains an unanswered question with crucial implications for the mechanisms and control of HBV infection.…”