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

Hayes, C. Nelson; Zhang, Yizhou; Makokha, Grace Naswa; Hasan, Zobaer; Omokoko, Magot Diata; Chayama, Kazuaki

doi:10.1111/jgh.13175

Cited by 33 publications

(28 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HBV entry into the host cell is the critical step in their life cycle. This process includes particle delivery and capture, complex internalization, and membrane fusion (Hayes et al, 2016). HBV entry requires a tightly coordinated group of specific viral proteins and multiple host receptors (Miao et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

E-cadherin Plays a Role in Hepatitis B Virus Entry Through Affecting Glycosylated Sodium-Taurocholate Cotransporting Polypeptide Distribution

Zhang

Duan

et al. 2020

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Hepatitis B virus (HBV) infection is a major cause of chronic liver disease and hepatocellular carcinoma. Current antiviral therapy does not effectively eradicate HBV and further investigations into the mechanisms of viral infection are needed to enable the development of new therapeutic agents. The sodium-taurocholate cotransporting polypeptide (NTCP) has been identified as a functional receptor for HBV entry in liver cells. However, the NTCP receptor is not sufficient for entry and other membrane proteins contribute to modulate HBV entry. This study seeks to understand how the NTCP functions in HBV entry. Herein we show that knockdown of the cell-cell adhesion molecule, E-cadherin significantly reduced infection by HBV particles and entry by HBV pseudoparticles in infected liver cells and cell lines. The glycosylated NTCP localizes to the plasma membrane through interaction with E-cadherin, which increases interaction with the preS1 portion of the Large HBV surface antigen. Our study contributes novel insights that advance knowledge of HBV infection at the level of host cell binding and viral entry.

show abstract

Section: Discussionmentioning

confidence: 99%

E-cadherin Plays a Role in Hepatitis B Virus Entry Through Affecting Glycosylated Sodium-Taurocholate Cotransporting Polypeptide Distribution

Zhang

Duan

et al. 2020

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…The discovery that sodium taurocholate co-transporting polypeptide (NTCP) acts as a receptor for HBV 6,7 enabled the development of in vitro culture systems that support the complete HBV replication cycle. HBV encodes three envelope glycoproteins, small (S), middle (M) and large(L) 8 . The preS1 domain of the L protein binds heparan sulfate proteoglycan (HSPG) 9–11 that precedes high-affinity virus interaction with NTCP.…”

Section: Introductionmentioning

confidence: 99%

Synchronized infection identifies early rate-limiting steps in the hepatitis B virus life cycle

Chakraborty

Henning

et al. 2020

Preprint

View full text Add to dashboard Cite

24Hepatitis B virus (HBV) is an enveloped DNA virus that contains a partially double-stranded relaxed circular (rc) 25 DNA. Upon infection, rcDNA is delivered to the nucleus where it is repaired to covalently closed circular (ccc) DNA 26 that serves as the transcription template for all viral RNAs. Our understanding of HBV particle entry dynamics and 27 host pathways regulating intracellular virus trafficking and cccDNA formation is limited. The discovery of sodium 28 taurocholate co-transporting peptide (NTCP) as the primary receptor allows studies on these early steps in viral 29 life cycle. We employed a synchronized infection protocol to quantify HBV entry kinetics. HBV attachment to cells 30 at 4°C is independent of NTCP, however, subsequent particle uptake is NTCP-dependent and reaches saturation 31 at 12h post-infection. HBV uptake is clathrin-and dynamin dependent with actin and tubulin playing a role in the 32 first 6h of infection. Cellular fractionation studies demonstrate HBV DNA in the nucleus within 6h of infection and 33 cccDNA was first detected at 24h post-infection. Our studies show the majority (83%) of cell bound particles enter 34 HepG2-NTCP cells, however, only a minority (<1%) of intracellular rcDNA was converted to cccDNA, highlighting 35 this as a rate-limiting in establishing infection in vitro. This knowledge highlights the deficiencies in our in vitro cell 36 culture systems and will inform the design and evaluation of physiologically relevant models that support efficient 37 HBV replication. 39Hepatitis B Virus (HBV) infects 257 million individuals worldwide and is a major driver of end-stage liver disease, 41 cirrhosis, and hepatocellular carcinoma (HCC). HBV is an enveloped DNA and prototypic member of the 42 hepadnaviridae that establishes its genome as an episomal, covalently closed circular DNA (cccDNA) in the nucleus 43 of infected hepatocytes. Current treatments suppress viral replication but are not curative, largely due to the 44 persistence of the cccDNA transcriptional template and failure to mount an effective anti-viral immune response 1 . 45In most cases, treatment is life-long and patients may still develop HCC 2 , highlighting a clinical need for new 46 curative therapies 3 . Despite its central role in the HBV life cycle our understanding of the host factors regulating 47 cccDNA genesis and half-life is limited 4 . 49Viral entry into a host cell represents the first step in the infectious life cycle and is mediated via specific 50 interactions between virus encoded proteins and cellular receptors that define internalization pathways 5 . The 51 discovery that sodium taurocholate co-transporting polypeptide (NTCP) acts as a receptor for HBV 6,7 enabled the 52 development of in vitro culture systems that support the complete HBV replication cycle. HBV encodes three 53 envelope glycoproteins, small (S), middle (M) and large(L) 8 . The preS1 domain of the L protein binds heparan 54 sulfate proteoglycan (HSPG) 9-11 that precedes high-affinity virus interaction with NTCP....

show abstract

“…HBV is an enveloped DNA virus which belongs to the hepadnaviridae family. Upon the entry of HBV into hepatocyte, the 3.2‐kb partially double‐stranded, relaxed circular DNA (rcDNA) is converted into a covalently closed circular DNA minichromosome (cccDNA) in the nucleus . The cccDNA is the template of transcription for the terminally redundant 3.5‐kb pregenomic RNA (pgRNA) and other sub‐genomic RNAs including 3.5‐kb precore RNA, 2.4‐kb preS1 RNA, 2.1‐kb preS2/S RNA, and 0.7‐kb X RNA .…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA GAS5 does not regulate HBV replication

Feng

et al. 2019

Journal of Medical Virology

View full text Add to dashboard Cite

Hepatitis B virus (HBV) infection remains a severe health burden worldwide.Emerging long noncoding RNAs (lncRNAs) are hijacked to enhance virus replication or employed by the host to stimulate immune responses to clear the virus. LncRNA growth arrest-specific transcript 5 (GAS5) can regulate RNA virus by suppressing the replication of both hepatitis C virus and human immunodeficiency virus. In this study, we explored the changes of HBV replication by overexpressing or knocking down GAS5 in HepAD38 cell and HepG2 cell transfected with pHBV1.2. We found HBV can induce the expression of GAS5. However, GAS5 had no effect on extracellular HBsAg and HBeAg, nor intracellular HBV RNA and HBV DNA. In addition, GAS5 possessed similar expression levels between stable HBV-producing cell lines and hepatoma cell lines. Furthermore, GAS5 showed no difference between healthy subjects and patients with chronic HBV in multiple GEO microarray data sets by GEO2R analysis.Taken together these results, GAS5 does not modulate the replication of HBV but it inhibits cell proliferation in HepAD38. This provides insights into the possible roles of GAS5 in HBV infection. K E Y W O R D Sbioinformatics, growth arrest-specific transcript 5, hepatitis B virus, replication

show abstract

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

Cited by 33 publications

References 76 publications

E-cadherin Plays a Role in Hepatitis B Virus Entry Through Affecting Glycosylated Sodium-Taurocholate Cotransporting Polypeptide Distribution

E-cadherin Plays a Role in Hepatitis B Virus Entry Through Affecting Glycosylated Sodium-Taurocholate Cotransporting Polypeptide Distribution

Synchronized infection identifies early rate-limiting steps in the hepatitis B virus life cycle

Long noncoding RNA GAS5 does not regulate HBV replication

Contact Info

Product

Resources

About