Extracellular HBV RNAs are heterogeneous in length and circulate as virions and capsid-antibody-complexes in chronic hepatitis B patients

Abstract

16Extracellular HBV RNA has been detected in both HBV-replicating cell culture media 17 and sera from chronic hepatitis B (CHB) patients, but its exact origin and composition 18 remain controversial. Here, we demonstrated that extracellular HBV RNA species 19 were of heterogeneous lengths, ranging from the length of pregenomic RNA to a few 20 hundred nucleotides. In cell models, these RNAs were predominantly associated with 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/320994 doi: bioRxiv preprint first posted online May. 13, 2018;

Hepatitis B Virus Virions Produced Under Nucleos(t)ide Analogue Treatment Are Mainly Not Infectious Because of Irreversible DNA Chain Termination

“…HBV belongs to the Hepadnavividae family and contains different forms of genome in virions. The Dane particles contain a partial double‐strand relaxed circular (rc) DNA of ~3.2 kilobases in length, while a small fraction of virions contain pregenomic (pg) RNA or the reverse‐transcription intermediates, that is, a 3′ truncated pgRNA and a short minus‐strand DNA …”

“…pregenomic (pg) RNA or the reverse-transcription intermediates, that is, a 3′ truncated pgRNA and a short minus-strand DNA. (5,6) During HBV infection, the virion enters hepatocyte by binding to its specific receptor, sodium taurocholate cotransporting polypeptide (NTCP). (7) Then, the rcDNA was converted to covalently closed circular DNA (cccDNA) in the nuclei of hepatocyte to serve as the template for transcription of viral RNAs, including pgRNA, which can be used as either mRNA for viral core protein and polymerase protein (P protein) or the template of reverse-transcriptional replication of viral DNA.…”

Treatment of Chronic Hepatitis B Virus Infection Using Small Molecule Modulators of Nucleocapsid Assembly: Recent Advances and Perspectives

“…47 The mature nucleocapsids containing rcDNA are then transferred to post-endoplasmic reticulum (ER) or pre-Golgi membranes, enveloped into virions and released from hepatocytes, 48 or recycled to the nucleus to amplify the cccDNA pool 49 (Figure 1A). The immature capsids, such as empty capsids 50,51 and capsids with incomplete HBV RNA/DNA fragments, 52 could be either released as naked capsids in the form of capsid-antibody complexes (CAC) 53 from hepatocytes or enveloped to form virus-like particles (Figure 1B). Recently, HBV virion production was found to be associated with autophagy.…”

Host Cell Rab GTPases in Hepatitis B Virus Infection

“…Accordingly, capsids/NCs must exist in vivo , but may be quickly removed from extracellular fluids. Indeed, naked capsids/NCs carrying HBV-specific DNA and RNA species were recently detected in the blood of HBV patients as capsid-antibody-complexes ( Bai et al, 2018 ). Since naked capsids/NCs are able to bind to cell surface-exposed HSPGs and competent for clathrin-mediated endocytosis, their uptake may enhance transmission of HBV genomes ( Cooper and Shaul, 2006 ).…”

“…SVPs greatly outnumber mature virions and presumably act as decoys to the immune system, as they are able to adsorb antibodies that might otherwise target viral particles ( Patient et al, 2009 ; Prange, 2012 ; Blondot et al, 2016 ). Naked capsids/NCs can carry HBV-specific DNA and RNA species and may be instrumental in spreading infection ( Bai et al, 2018 ). HBV exploits different intracellular trafficking routes and diverse host factors in order to release its particle types ( Patient et al, 2009 ; Prange, 2012 ).…”