Production of infectious dromedary camel hepatitis E virus by a reverse genetic system: Potential for zoonotic infection

Li, Tiancheng; Zhou, Xianfeng; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Nakamura, Tomofumi; Takeda, Naokazu; Wakita, Takaji

doi:10.1016/j.jhep.2016.07.013

Cited by 52 publications

(58 citation statements)

References 36 publications

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“…E). In addition, an HEV‐induced IFN response was further confirmed using in vitro generated Gt1 HEV and dromedary camel HEV (Gt7) (Fig. F‐I; http://onlinelibrary.wiley.com/doi/10.1002.hep.29702/suppinfo).…”

Section: Resultsmentioning

confidence: 71%

The RNA genome of hepatitis E virus robustly triggers an antiviral interferon response

Wang

et al. 2018

Hepatology

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HEV infection elicits an active IFN-related antiviral response in vitro and in patients, triggered by the viral RNA and mediated by IFN regulatory factors 3 and 7 and the Janus kinase-signal transducer and activator of transcription cascade; these findings have revealed new insights into HEV-host interactions and provided the basis for understanding the pathogenesis and outcome of HEV infection. (Hepatology 2018;67:2096-2112).

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Section: Resultsmentioning

confidence: 71%

The RNA genome of hepatitis E virus robustly triggers an antiviral interferon response

Wang

et al. 2018

Hepatology

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“…B). Both the RNA and capsid protein appeared in the same fractions, and the density of the virion was similar to that of G7 HEV, indicating that these fractions contained complete G5 HEV particles. Although we were unable to observe the virus particles by electron microscopy, fractions 8 and 9 could induce G5 HEV infection in PLC/PRF/5 cells (data not shown), demonstrating that the G5 HEV purified from the cell culture supernatants is infectious.…”

Section: Resultsmentioning

confidence: 80%

“…To answer this question, we used a reverse genetics system to produce infectious G5 HEV. Because PLC/PRF/5 cells have been shown to permit the growth of several HEV strains and infectious G7 HEV has been successfully recovered by a reverse genetics system, we examined cell lines for the G5 HEV RNA transfection and confirmed that infectious G5 HEV could be produced not only in PLC/PRF/5 cells but also in A549 and HepG2/C3A cells.…”

Section: Discussionmentioning

confidence: 80%

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Genotype 5 Hepatitis E Virus Produced by a Reverse Genetics System Has the Potential for Zoonotic Infection

Bai

Yoshizaki

et al. 2018

Hepatol Commun

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Neither an animal model nor a cell culture system has been established for the genotype 5 hepatitis E virus (G5 HEV), and the pathogenicity, epidemiology, and replication mechanism of the virus remain unclear. In this study, we used a reverse genetics system to generate G5 HEV and examined the possibility of zoonotic infection. Capped and uncapped genomic G5 HEV RNAs generated by in vitro transcription were transfected into PLC/PRF/5 cells. Infectious G5 HEV was recovered from the capped G5 HEV RNA–transfected PLC/PRF/5 cells and the subsequently passaged cells. G5 HEV was also recovered from uncapped G5 HEV–transfected PLC/PRF/5 cells after a longer lag phase, suggesting that the 5′‐cap structure is not essential but affected the efficiency of G5 HEV replication. G5 HEV infection was neutralized not only by anti‐G5 HEV‐like particles (HEV‐LPs) antibody, but also by anti‐G1, anti‐G3, anti‐G4, and anti‐G7 HEV‐LPs antibodies. G5 HEV was capable of infecting cynomolgus monkeys negative for anti‐HEV antibody but not animals positive for anti‐G7 HEV immunoglobulin G (IgG), indicating that cynomolgus monkeys were susceptible to G5 HEV, and the serotype of G5 HEV was identical to that of G7 HEV and human HEVs. Moreover, G5 HEV replication was efficiently inhibited by ribavirin and partially inhibited by sofosbuvir. Conclusion: Infectious G5 HEV was produced using a reverse genetics system, and the antigenicity was identical to that of human HEVs and G7 HEV. Transmission of G5 HEV to primates was confirmed by an experimental infection, providing evidence of the possibility of zoonotic infection by G5 HEV.

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“…An HEV strain that belongs to G7 has also been isolated from a hepatitis E patient, suggesting that the DcHEV could cause zoonotic infection in humans (Lee et al, 2016). A recent study indicated that the DcHEV generated by a reverse genetic system resulted in HEV infection in cynomolgus monkeys, providing new evidence of zoonotic infection by DcHEV (Li et al, 2016b). A long-term epidemiological study confirmed that the partial DcHEV genome were detected in camel serum or fecal samples obtained in the UAE, Somalia, Kenya, and Pakistan during the period 1983-2015, suggesting that DcHEV in dromedary camels is long established, diversified and geographically widespread (Rasche et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Serological evidence of hepatitis E virus infection in dromedary camels in Ethiopia

Yoshizaki

Zhou

et al. 2017

Journal of Virological Methods

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Production of infectious dromedary camel hepatitis E virus by a reverse genetic system: Potential for zoonotic infection

Cited by 52 publications

References 36 publications

The RNA genome of hepatitis E virus robustly triggers an antiviral interferon response

The RNA genome of hepatitis E virus robustly triggers an antiviral interferon response

Genotype 5 Hepatitis E Virus Produced by a Reverse Genetics System Has the Potential for Zoonotic Infection

Serological evidence of hepatitis E virus infection in dromedary camels in Ethiopia

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