pH-independent entry and sequential endosomal sorting are major determinants of hepadnaviral infection in primary hepatocytes

Funk, Anneke; Mhamdi, Mouna; Hohenberg, Heinz; Will, Hans; Sirma, Hueseyin

doi:10.1002/hep.21297

Cited by 23 publications

(26 citation statements)

References 29 publications

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“…However, the weight of data favours pH-independent entry as well as an endocytic mechanism and shows that the virus does not require passage through a highly acidic compartment. The effect of the vATPase inhibitors seem to be due more to effects on viral trafficking inside the cell than on the endosomal pH alone [34] . After the virus is taken up by the cell via endocytosis, it has to be transported to the nucleus to establish infection.…”

Section: In Vitro Infectionmentioning

confidence: 98%

“…1 h after attachment only about 70% of bound DHBV was taken up and internalization was complete within 3 h. This shows that virus uptake itself takes a relatively long time period, but since after 3 h all bound virions were internalized, uptake is very efficient. In contrast, viral trafficking inside the cell does not seem to be efficient since a high proportion of viral particles are degraded after viral entry into the cell and thus cannot establish infection [34] . It has been shown previously that DHBV entry into PDHs requires energy, which indicates that cellular and/ or viral processes actively take place and that DHBV is presumably entering the cell via endocytosis [33,34] .…”

Section: In Vitro Infectionmentioning

confidence: 99%

“…In contrast, viral trafficking inside the cell does not seem to be efficient since a high proportion of viral particles are degraded after viral entry into the cell and thus cannot establish infection [34] . It has been shown previously that DHBV entry into PDHs requires energy, which indicates that cellular and/ or viral processes actively take place and that DHBV is presumably entering the cell via endocytosis [33,34] . Studies addressing the pH-dependency of DHBV infection by the use of chemical substances that increase endosomal pH led to contradicting results [33,[88][89][90] .…”

Section: In Vitro Infectionmentioning

confidence: 99%

“…unknown cellular receptor compounds. After binding, viral particles are taken up into the cell by receptor-mediated endocytosis [32][33][34] . Then, the nucleocapsid is released from the endosomal compartment into the cytosol.…”

Section: Overviewmentioning

confidence: 99%

See 3 more Smart Citations

Avian hepatitis B viruses: Molecular and cellular biology, phylogenesis, and host tropism

Funk

Mhamdi²,

Will³

et al. 2007

WJG

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The human hepatitis B virus (HBV) and the duck hepatitis B virus (DHBV) share several fundamental features. Both viruses have a partially double-stranded DNA genome that is replicated via a RNA intermediate and the coding open reading frames (ORFs) overlap extensively. In addition, the genomic and structural organization, as well as replication and biological characteristics, are very similar in both viruses. Most of the key features of hepadnaviral infection were first discovered in the DHBV model system and subsequently confirmed for HBV. There are, however, several differences between human HBV and DHBV. This review will focus on the molecular and cellular biology, evolution, and host adaptation of the avian hepatitis B viruses with particular emphasis on DHBV as a model system.

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Section: In Vitro Infectionmentioning

confidence: 98%

Section: In Vitro Infectionmentioning

confidence: 99%

Section: In Vitro Infectionmentioning

confidence: 99%

Section: Overviewmentioning

confidence: 99%

See 2 more Smart Citations

Avian hepatitis B viruses: Molecular and cellular biology, phylogenesis, and host tropism

Funk

Mhamdi²,

Will³

et al. 2007

WJG

Self Cite

View full text Add to dashboard Cite

show abstract

“…46 However, in the case of duck hepatitis B virus (DHBV), pharmacological agents that raise the pH in the endocytic pathway did not affect infection. 47,48 While the vacuolar proton-ATPase acidifies the endosomal compartment, 48 vacuolar proton-ATPase not only lowers the vesicular pH but also generates an internal positive electrical potential across the membrane, 49 suggesting that membrane potentialdependent, but pH-independent, sorting and transportation of the virus within and beyond the early endosome is necessary for hepadnavirus infection to be established. 48 Endo-lysosomal pathway.…”

mentioning

confidence: 99%

Early events in hepatitis B virus infection: From the cell surface to the nucleus

Hayes

Zhang

Makokha

et al. 2016

J of Gastro and Hepatol

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While most adults are able to clear acute hepatitis B virus (HBV) infection, chronic HBV infection is recalcitrant to current therapy because of the persistence of covalently closed circular DNA in the nucleus. Complete clearance of the virus in these patients is rare, and long-term therapy with interferon and/or nucleoside analogues may be required in an attempt to suppress viral replication and prevent progressive liver damage. The difficulty of establishing HBV infection in cell culture and experimental organisms has hindered efforts to elucidate details of the HBV life cycle, but it has also revealed the importance of the cellular microenvironment required for HBV binding and entry. Recent studies have demonstrated an essential role of sodium-taurocholate cotransporting polypeptide as a functional receptor in HBV infection, which has facilitated the development of novel infection systems and opened the way for more detailed understanding of the early steps of HBV infection as well as a potential new therapeutic target. However, many gaps remain in understanding of how HBV recognizes and attaches to hepatocytes prior to binding to sodium-taurocholate cotransporting polypeptide, as well as events that are triggered after binding, including entry into the cell, intracellular transport, and passage through the nuclear pore complex. This review summarizes current knowledge of the initial stages of HBV infection leading to the establishment of covalently closed circular DNA in the nucleus.

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Visualization of hepatitis B virus entry – novel tools and approaches to directly follow virus entry into hepatocytes

et al. 2016

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Hepatitis B virus (HBV) is a widespread human pathogen, responsible for chronic infections of ca. 240 million people worldwide. Until recently, the entry pathway of HBV into hepatocytes was only partially understood. The identification of human sodium taurocholate cotransporting polypeptide (NTCP) as a bona fide receptor of HBV has provided us with new tools to investigate this pathway in more details. Combined with advances in virus visualization techniques, approaches to directly visualize HBV cell attachment, NTCP interaction, virion internalization and intracellular transport are now becoming feasible. This review summarizes our current understanding of how HBV specifically enters hepatocytes, and describes possible visualization strategies applicable for a deeper understanding of the underlying cell biological processes.

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pH-independent entry and sequential endosomal sorting are major determinants of hepadnaviral infection in primary hepatocytes

Cited by 23 publications

References 29 publications

Avian hepatitis B viruses: Molecular and cellular biology, phylogenesis, and host tropism

Avian hepatitis B viruses: Molecular and cellular biology, phylogenesis, and host tropism

Early events in hepatitis B virus infection: From the cell surface to the nucleus

Visualization of hepatitis B virus entry – novel tools and approaches to directly follow virus entry into hepatocytes

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