Long-Term Hepatitis B Virus Infection Induces Cytopathic Effects in Primary Human Hepatocytes, and Can Be Partially Reversed by Antiviral Therapy

Zai, Wenjing; Hu, Kongying; Ye, Jianyu; Ding, Jiahui; Huang, Chao; Li, Yaming; Fang, Zhong; Wu, Min; Chen, Jieliang; Yuan, Zhenghong

doi:10.1128/spectrum.01328-21

Cited by 12 publications

(9 citation statements)

References 49 publications

(59 reference statements)

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“…The endurance of electrophoretic mobility alterations induced by PAC-A dimers and trimers on HSV gD and gB, as well as on IV HA1, upon boiling of protein samples in SDS sample buffer, sustains the view that the exposure of purified viral glycoproteins to PAC-As results in the formation of covalent linkages between PAC-As molecules and viral proteins [ 186 , 188 ]. These covalent interactions may result in protein-protein crosslinking, as most PACs have two or more reactive quinone moieties [ 283 ]; this would explain the smearing and disappearance of glycoprotein bands that we and others have observed in electrophoretic mobility shift assay experiments with purified viral glycoproteins [ 186 , 188 , 204 , 215 , 243 ].…”

Section: Discussionmentioning

confidence: 99%

“…For both viruses, after a possible acute phase, viral infection may progress in chronicity. During chronic infection, viral cytopathic effects combined with the cell damage due to the immune response may promote liver cirrhosis and hepatocellular carcinoma [ 215 ]. Although effective therapies for the treatment of HBV and HCV infection are available, with a clear improvement of patient treatments and the cure of the infection, at least for HCV, the high costs of the therapy and the risk of drug failure still prompt to the search and development of new drugs.…”

Section: The Broad-spectrum Antiviral Activity Of A-type Pacsmentioning

confidence: 99%

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Tackling the Future Pandemics: Broad-Spectrum Antiviral Agents (BSAAs) Based on A-Type Proanthocyanidins

2022

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A-type proanthocyanidins (PAC-As) are plant-derived natural polyphenols that occur as oligomers or polymers of flavan-3-ol monomers, such as (+)-catechin and (−)-epicatechin, connected through an unusual double A linkage. PAC-As are present in leaves, seeds, flowers, bark, and fruits of many plants, and are thought to exert protective natural roles against microbial pathogens, insects, and herbivores. Consequently, when tested in isolation, PAC-As have shown several biological effects, through antioxidant, antibacterial, immunomodulatory, and antiviral activities. PAC-As have been observed in fact to inhibit replication of many different human viruses, and both enveloped and non-enveloped DNA and RNA viruses proved sensible to their inhibitory effect. Mechanistic studies revealed that PAC-As cause reduction of infectivity of viral particles they come in contact with, as a result of their propensity to interact with virion surface capsid proteins or envelope glycoproteins essential for viral attachment and entry. As viral infections and new virus outbreaks are a major public health concern, development of effective Broad-Spectrum Antiviral Agents (BSAAs) that can be rapidly deployable even against future emerging viruses is an urgent priority. This review summarizes the antiviral activities and mechanism of action of PAC-As, and their potential to be deployed as BSAAs against present and future viral infections.

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Section: Discussionmentioning

confidence: 99%

Section: The Broad-spectrum Antiviral Activity Of A-type Pacsmentioning

confidence: 99%

Tackling the Future Pandemics: Broad-Spectrum Antiviral Agents (BSAAs) Based on A-Type Proanthocyanidins

2022

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“…In CHB patients, fibronectin levels in plasma have been demonstrated to be a predictor of HBsAg clearance (Liu et al, 2019). Long-term HBV infection has been shown to lead to cellular proteome remodeling, which can mediate the pathological effect (Zai et al, 2022). Through the mass The expression of ficolin-2 (FCN2) and carboxypeptidase B2 (CPB2) was different in CHB patients with different fibrosis stages.…”

Section: Proteomicsmentioning

confidence: 99%

Advances in multi-omics research on viral hepatitis

Xiang

et al. 2022

Front. Microbiol.

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Viral hepatitis is a major global public health problem that affects hundreds of millions of people and is associated with significant morbidity and mortality. Five biologically unrelated hepatotropic viruses account for the majority of the global burden of viral hepatitis, including hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). Omics is defined as the comprehensive study of the functions, relationships and roles of various types of molecules in biological cells. The multi-omics analysis has been proposed and considered key to advancing clinical precision medicine, mainly including genomics, transcriptomics and proteomics, metabolomics. Overall, the applications of multi-omics can show the origin of hepatitis viruses, explore the diagnostic and prognostics biomarkers and screen out the therapeutic targets for viral hepatitis and related diseases. To better understand the pathogenesis of viral hepatitis and related diseases, comprehensive multi-omics analysis has been widely carried out. This review mainly summarizes the applications of multi-omics in different types of viral hepatitis and related diseases, aiming to provide new insight into these diseases.

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“…This means that some compositions block the signaling pathway necessary for the HBV life cycle or that some compositions are lacking support. The expression of HBV can be maintained for a long time, although primary human hepatocytes (PHHs) are infected with HBV in the medium with Forskolin [ 86 ]. However, Forskolin may repress the expression of NTCP to suppress HBV infection in PDO culture (Fig.…”

Section: Liver Organoids For Carcinogenesis Researchmentioning

confidence: 99%

Liver organoids: an in vitro 3D model for liver cancer study

Zhang

Dong

2022

Cell Biosci

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Primary liver cancer (PLC) is the second leading cause of cancer mortality worldwide, and its morbidity unceasingly increases these years. Hepatitis B virus (HBV) infection accounted for approximately 50% of hepatocellular carcinoma (HCC) cases globally in 2015. Due to the lack of an effective model to study HBV-associated liver carcinogenesis, research has made slow progress. Organoid, an in vitro 3D model which maintains self-organization, has recently emerged as a powerful tool to investigate human diseases. In this review, we first summarize the categories and development of liver organoids. Then, we mainly focus on the functions of culture medium components and applications of organoids for HBV infection and HBV-associated liver cancer studies. Finally, we provide insights into a potential patient-derived organoid model from those infected with HBV based on our study, as well as the limitations and future applications of organoids in liver cancer research.

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Long-Term Hepatitis B Virus Infection Induces Cytopathic Effects in Primary Human Hepatocytes, and Can Be Partially Reversed by Antiviral Therapy

Cited by 12 publications

References 49 publications

Tackling the Future Pandemics: Broad-Spectrum Antiviral Agents (BSAAs) Based on A-Type Proanthocyanidins

Tackling the Future Pandemics: Broad-Spectrum Antiviral Agents (BSAAs) Based on A-Type Proanthocyanidins

Advances in multi-omics research on viral hepatitis

Liver organoids: an in vitro 3D model for liver cancer study

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