Establishment and Characterization of an HBV Viral Spread and Infectious System following Long-Term Passage of an HBV Clinical Isolate in the Primary Human Hepatocyte and Fibroblast Coculture System

Liu, Yang; Kornyeyev, Dmytro; May, Lindsey; Han, Dong; Aeschbacher, Thomas; Chang, Silvia; Martin, Ross; Mo, Hongmei; Feierbach, Becket

doi:10.1128/jvi.00849-22

Cited by 2 publications

(1 citation statement)

References 32 publications

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“…39 Thus although HBeAg expression is critical for the induction of IT for the establishment of chronic HBV infection in vivo, 4 BCP mutations increase genome replication, [14][15][16]24 which should augment virion production. Indeed a recent report found the ability of G1764A/C1766T BCP mutations (not the common A1762T/ G1764A mutations) to markedly enhance infectivity of a genotype A isolate in PHHs co-cultured with human fibroblasts, 40 apparently by more efficient spreading to adjacent hepatocytes because such mutations should not influence viral entry.…”

Section: Peg Could Enhance Shbv Infectivity Especially Following Prol...mentioning

confidence: 99%

Clinical isolates of hepatitis B virus genotype C have higher in vitro transmission efficiency than genotype B isolates

Chen

et al. 2023

Journal of Medical Virology

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Serum samples were collected from 54 hepatitis B e antigen (HBeAg)positive Chinese patients infected with hepatitis B virus (HBV) subgenotype B2 or C2. They were compared for transmission efficiency using same volume of samples or infectivity using same genome copy number. Adding polyethylene glycol (PEG) during inoculation did not increase infectivity of fresh samples but markedly increased infectivity following prolonged sample storage. Differentiated HepaRG cells infected without PEG produced more hepatitis B surface antigen (HBsAg) and higher HBsAg/HBeAg ratio than sodium taurocholate cotransporting polypeptide (NTCP)-reconstituted HepG2 cells infected with PEG. They better supported replication of core promoter mutant in contrast to wild-type (WT) virus by HepG2/NTCP cells. Overall, subgenotype C2 samples had higher viral load than B2 samples, and in general produced more HBeAg, HBsAg, and replicative DNA following same-volume inoculation. Precore mutant was more prevalent in subgenotype B2 and had reduced transmission efficiency. When same genome copy number of viral particles was inoculated, viral signals were not necessarily higher for three WT C2 isolates than four WT B2 isolates. Using viral particles generated from cloned HBV genome, three WT C2 isolates showed slightly reduced infectivity than three B2 isolates. In conclusion, subgenotype C2 serum samples had higher transmission efficiency than B2 isolates in association with higher viral load and lower prevalence of precore mutant, but not necessarily higher infectivity. PEGindependent infection by HBV viremic serum samples is probably attributed to a labile host factor.

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Section: Peg Could Enhance Shbv Infectivity Especially Following Prol...mentioning

confidence: 99%

Clinical isolates of hepatitis B virus genotype C have higher in vitro transmission efficiency than genotype B isolates

Chen

et al. 2023

Journal of Medical Virology

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Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis

Schollmeier

Glitscher

Hildt

2023

IJMS

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The hepatitis B virus (HBV) counts as a major global health problem, as it presents a significant causative factor for liver-related morbidity and mortality. The development of hepatocellular carcinomas (HCC) as a characteristic of a persistent, chronic infection could be caused, among others, by the pleiotropic function of the viral regulatory protein HBx. The latter is known to modulate an onset of cellular and viral signaling processes with emerging influence in liver pathogenesis. However, the flexible and multifunctional nature of HBx impedes the fundamental understanding of related mechanisms and the development of associated diseases, and has even led to partial controversial results in the past. Based on the cellular distribution of HBx—nuclear-, cytoplasmic- or mitochondria-associated—this review encompasses the current knowledge and previous investigations of HBx in context of cellular signaling pathways and HBV-associated pathogenesis. In addition, particular focus is set on the clinical relevance and potential novel therapeutic applications in the context of HBx.

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Establishment and Characterization of an HBV Viral Spread and Infectious System following Long-Term Passage of an HBV Clinical Isolate in the Primary Human Hepatocyte and Fibroblast Coculture System

Abstract: The existing cell culture-based methods to study HBV have limitations and do not allow for viral long-term passage. In this study, an HBV genotype A clinical isolate was subjected to multiple rounds of UV treatment and passaged in an optimized PHH/human fibroblast coculture system.

Cited by 2 publications

References 32 publications

Clinical isolates of hepatitis B virus genotype C have higher in vitro transmission efficiency than genotype B isolates

Clinical isolates of hepatitis B virus genotype C have higher in vitro transmission efficiency than genotype B isolates

Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis

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