The Hepatitis E Virus Capsid C-Terminal Region Is Essential for the Viral Life Cycle: Implication for Viral Genome Encapsidation and Particle Stabilization

Shiota, Tomoyuki; Li, Tiancheng; Yoshizaki, Sayaka; Kato, Takanobu; Wakita, Takaji; Ishii, Koji

doi:10.1128/jvi.00444-13

Cited by 53 publications

(46 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The replication efficiencies of these new systems are several orders of magnitude higher than those of previous culturing systems (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). The increased availability of HEV reagents provided by the new culturing systems has permitted many groups to construct HEV infectious clones, thereby facilitating multiple recent reverse genetic studies (34)(35)(36)(37)(38). PLC/PRF/5 cells obtained from the Japanese Collection of Research Bioresources (cell number, JCRB0406; lot number, 01272003; Osaka, Japan) were first characterized for HEV infection in our laboratory.…”

mentioning

confidence: 99%

Establishment of hepatitis E virus infection‐permissive and ‐non‐permissive human hepatoma PLC/PRF/5 subclones

Shiota

Yoshizaki

et al. 2015

Microbiology and Immunology

Self Cite

View full text Add to dashboard Cite

PLC/PRF/5 cells show limited permissiveness, meaning that almost all subclones are permissive; however, some subclones do not exhibit permissiveness for hepatitis E virus (HEV) infection. In this study, the single-cell cloning of PLC/PRF/5 was performed and heterogeneous subclones characterized. Notably, the efficiency of intracellular virus replication did not correlate with the permissiveness for HEV infection. However, as well as binding permissive subclones, virus-like particles bound non-permissive subclones on various levels, suggesting that these subclones have some deficiencies in the attachment and entry steps of infection. Our data would be useful for investigating the HEV life cycle.

show abstract

mentioning

confidence: 99%

Establishment of hepatitis E virus infection‐permissive and ‐non‐permissive human hepatoma PLC/PRF/5 subclones

Shiota

Yoshizaki

et al. 2015

Microbiology and Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…To analyse the effect of silvestrol against HEV, we first transfected the human hepatoma cell line Huh7.5 with different HEV subgenomic replicons, in which a part of the ORF2 was replaced by a Gaussia luciferase reporter gene. These include the HEV gt 3 construct p6 (Shukla et al, 2011), a variant (G1634R) thereof with increased replication fitness (Debing et al, 2014;Todt et al, 2016a), the gt3-based wild boar isolate 83-2-27 (Shiota et al, 2013) and the gt 1 strain Sar55 harboring an S17 insertion in the ORF1 like the p6 strain (Shukla et al, 2011). As depicted in Fig.…”

Section: Antiviral Activity Of Silvestrol Against Subgenomic Hev Replmentioning

confidence: 99%

The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo

et al. 2018

View full text Add to dashboard Cite

Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in the family Hepeviridae. HEV infections are the common cause of acute hepatitis but can also take chronic courses. Ribavirin is the treatment of choice for most patients and type I interferon (IFN) has been evaluated in a few infected transplantation patients in vivo. However, no effective and specific treatments against HEV infections are currently available. In this study, we evaluated the natural compound silvestrol, isolated from the plant Aglaia foveolata, and known for its specific inhibition of the DEAD-box RNA helicase eIF4A in state-of-the-art HEV experimental model systems. Silvestrol blocked HEV replication of different subgenomic replicons in a dose-dependent manner at low nanomolar concentrations and acted additive to ribavirin (RBV). In addition, HEV p6-based full length replication and production of infectious particles was reduced in the presence of silvestrol. A pangenotypic effect of the compound was further demonstrated with primary isolates from four different human genotypes in HEV infection experiments of hepatocyte-like cells derived from human embryonic and induced pluripotent stem cells. In vivo, HEV RNA levels rapidly declined in the feces of treated mice while no effect was observed in the vehicle treated control animals. In conclusion, silvestrol could be identified as pangenotypic HEV replication inhibitor in vitro with additive effect to RBV and further demonstrated high potency in vivo. The compound therefore may be considered in future treatment strategies of chronic hepatitis E in immunocompromised patients.

show abstract

“…In-depth knowledge of the capsid protein encoded by ORF2 has allowed the study of HEV interactions with target cells. It is believed that the C-terminal region of the ORF2 plays an important role in this stage of HEV life cycle [48]. This protein region first interacts with specific receptors on the cell membrane, including: heparan sulfate proteoglycans [49] and heat-shock protein cognate 70, facilitating virus binding to the hepatocyte.…”

Section: • • Hev Binding To Cell Processmentioning

confidence: 99%

Hepatitis E: Latest Developments in Knowledge

et al. 2016

View full text Add to dashboard Cite

Hepatitis E, caused by Hepatitis E virus (HEV), is a highly prevalent disease in developing countries. In developed nations, autochthonous HEV infections seem to be an emergent disease. Its clinical manifestations and epidemiology are well known for endemic countries. It has been confirmed that hepatitis E is a zoonosis and that parenteral transmission can also occur. The molecular mechanisms of HEV replication are not fully understood, mostly because there are no efficient cell culture systems. HEV can cause chronic hepatitis in organ transplant recipients and immunocompetent patients. Cases with fulminant hepatitis and other extrahepatic manifestations have also been reported. The diagnosis is based on serological studies and detection of HEV RNA in blood and feces. Treatment with ribavirin and/or pegylated-IFN-α have proven to be successful in some cases. The recently approved/marketed vaccine is a good option in order to prevent this infection.

show abstract

The Hepatitis E Virus Capsid C-Terminal Region Is Essential for the Viral Life Cycle: Implication for Viral Genome Encapsidation and Particle Stabilization

Cited by 53 publications

References 20 publications

Establishment of hepatitis E virus infection‐permissive and ‐non‐permissive human hepatoma PLC/PRF/5 subclones

Establishment of hepatitis E virus infection‐permissive and ‐non‐permissive human hepatoma PLC/PRF/5 subclones

The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo

Hepatitis E: Latest Developments in Knowledge

Contact Info

Product

Resources

About