Complete and Incomplete Hepatitis B Virus Particles: Formation, Function, and Application

Abstract

Hepatitis B virus (HBV) is a para-retrovirus or retroid virus that contains a double-stranded DNA genome and replicates this DNA via reverse transcription of a RNA pregenome. Viral reverse transcription takes place within a capsid upon packaging of the RNA and the viral reverse transcriptase. A major characteristic of HBV replication is the selection of capsids containing the double-stranded DNA, but not those containing the RNA or the single-stranded DNA replication intermediate, for envelopment during virion secretion. The complete HBV virion particles thus contain an outer envelope, studded with viral envelope proteins, that encloses the capsid, which, in turn, encapsidates the double-stranded DNA genome. Furthermore, HBV morphogenesis is characterized by the release of subviral particles that are several orders of magnitude more abundant than the complete virions. One class of subviral particles are the classical surface antigen particles (Australian antigen) that contain only the viral envelope proteins, whereas the more recently discovered genome-free (empty) virions contain both the envelope and capsid but no genome. In addition, recent evidence suggests that low levels of RNA-containing particles may be released, after all. We will summarize what is currently known about how the complete and incomplete HBV particles are assembled. We will discuss briefly the functions of the subviral particles, which remain largely unknown. Finally, we will explore the utility of the subviral particles, particularly, the potential of empty virions and putative RNA virions as diagnostic markers and the potential of empty virons as a vaccine candidate.

Characterization of Serum HBV RNA in Patients with Untreated HBeAg-Positive and -Negative Chronic Hepatitis B Infection

“…The current speculations include the immature RNAcontaining virion as a byproduct of normal HBV replication and exosome secretion (20). The current study data showed that the serum HBV RNA level was positively correlated with serum ALT and AST levels ( Figure 2).…”

Serum Hepatitis B Virus RNA: A New Potential Biomarker for Chronic Hepatitis B Virus Infection

“…Inside the capsid, the polymerase converts pgRNA into rcDNA through reverse transcription, followed by envelopment by HBV envelope proteins on the endoplasmic reticulum membrane for virion secretion through multivesicular bodies, or reentry into the nucleus to replenish the cccDNA pool. In addition to rcDNA, HBV reverse transcription produces a minor viral DNA species, double‐stranded linear DNA (dslDNA), which can be secreted as virion DNA and redirected into the nucleus to form cccDNA . However, dslDNA is often randomly integrated into the host genome through nonhomologous end joining, which may promote HCC development by inducing chromosomal instability, insertional mutagenesis of HBV genes, and HCC‐associated host genes .…”

Insights for clinical diagnostic indicators of virus and host in chronic hepatitis B infection

“…The production of empty virus can be induced by S protein alone while L protein is not necessary but can promote the secretion of empty virus, which may be one of the reasons why empty virus (10 11 IU/mL) are much more than complete virus (10 9 IU/mL) . The L protein, also located in the envelope of empty virus, can help virus enter hepatocytes like a mature Dane particle through sodium taurocholate cotransporting polypeptide (NTCP) receptor and regulate HBV re‐infection, or extracellularly, neutralize the anti‐HBs . The components, HBcAg and HBsAg, of empty virus might be the mirror of HBV replication and immune status.…”