Syntenin regulates hepatitis C virus sensitivity to neutralizing antibody by promoting E2 secretion through exosomes

Deng, Libin; Jiang, Wang; Wang, Xiaoning; Merz, Andreas; Hiet, Marie–Sophie; Chen, Yujie; Pan, Xiaoyu; Jiu, Yaming; Yu, Yang; Yu, Bowen; He, Yongning; Tu, Zhengkun; Niu, Junqi; Bartenschlager, Ralf; Long, Gang

doi:10.1016/j.jhep.2019.03.006

Cited by 35 publications

(33 citation statements)

References 45 publications

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“…Catanese et al [58] have shown that more copies of apoE were incorporated into the virion particle than the HCV structural protein E2 suggesting that apoE plays an important role in HCV attachment [58]. Deng et al [59] suggest that the HCV glycoprotein E2 together with syntenin might be components of exosomes derived from HCV infected cells. Syntenin, a host factor regulating the exosome biogenesis, has been found to promote HCV E2 secretion, while the production of infectious virions remained unaffected and thus appears to be a parallel process to HCV exosome release.…”

Section: Discussionmentioning

confidence: 99%

Mathematical modeling of hepatitis C RNA replication, exosome secretion and virus release

2020

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Hepatitis C virus (HCV) causes acute hepatitis C and can lead to life-threating complications if it becomes chronic. The HCV genome is a single plus strand of RNA. Its intracellular replication is a spatiotemporally coordinated process of RNA translation upon cell infection, RNA synthesis within a replication compartment, and virus particle production. While HCV is mainly transmitted via mature infectious virus particles, it has also been suggested that HCV-infected cells can secrete HCV RNA carrying exosomes that can infect cells in a receptor independent manner. In order to gain insight into these two routes of transmission, we developed a series of intracellular HCV replication models that include HCV RNA secretion and/or virus assembly and release. Fitting our models to in vitro data, in which cells were infected with HCV, suggests that initially most secreted HCV RNA derives from intracellular cytosolic plus-strand RNA, but subsequently secreted HCV RNA derives equally from the cytoplasm and the replication compartments. Furthermore, our model fits to the data suggest that the rate of virus assembly and release is limited by host cell resources. Including the effects of direct acting antivirals in our models, we found that in spite of decreasing intracellular HCV RNA and extracellular virus concentration, low level HCV RNA secretion may continue as long as intracellular RNA is available. This may possibly explain the presence of detectable levels of plasma HCV RNA at the end of treatment even in patients that ultimately attain a sustained virologic response.

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Section: Discussionmentioning

confidence: 99%

Mathematical modeling of hepatitis C RNA replication, exosome secretion and virus release

2020

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“…They showed that such EV were able to infect primary human hepatocytes as well as the human hepatoma cell line Huh7.5 . Recently, Deng et al demonstrated in vitro that the overexpression of Syntenin, a protein involved in the exosome secretion pathway, induced the release of EV containing hepatitis C virus (HCV) protein E2 . These EV could act as an antibody bait during HCV infection.…”

Section: Extracellular Vesicles In Chronic Liver Diseasesmentioning

confidence: 93%

“…EV were shown to be involved in hepatitis B, hepatitis C and hepatitis E propagation. Virions were demonstrated to spread to neighbouring cells using the exosome secretion pathways of hepatocytes . From sera of patients with chronic hepatitis C, Bukong et al, isolated EV containing replication competent viral RNA associated with miR122, Ago2 and HSP90.…”

Section: Extracellular Vesicles In Chronic Liver Diseasesmentioning

confidence: 99%

Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration

Balaphas

Meyer

Sadoul

et al. 2019

Liver International

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Extracellular vesicles are membrane fragments that can be produced by all cell types. Interactions between extracellular vesicles and various liver cells constitute an emerging field in hepatology and recent evidences have established a role for extracellular vesicles in various liver diseases and physiological processes. Extracellular vesicles originating from liver cells are implicated in intercellular communication and fluctuations of specific circulating extracellular vesicles could constitute new diagnostic tools. In contrast, extracellular vesicles derived from progenitor cells interact with hepatocytes or non‐parenchymal cells, thereby protecting the liver from various injuries and promoting liver regeneration. Our review focuses on recent developments investigating the role of various types of extracellular vesicles in acute and chronic liver diseases as well as their potential use as biomarkers and therapeutic tools.

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“…Another evasion method is through the use of decoys. Recently it has been reported that in a HCVcc system, infected cells produce lipid droplets coated with the E2 protein [119]. This may also be a strategy to subvert the immune system by using these E2-coated droplets to interact with nAbs, thereby reducing the availability of nAbs to target E2 present on the surface of the virus particle.…”

Section: Evading the Host Adaptive Immune Responsementioning

confidence: 99%

Hepatitis C Virus Vaccine: Challenges and Prospects

et al. 2020

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The hepatitis C virus (HCV) causes both acute and chronic infection and continues to be a global problem despite advances in antiviral therapeutics. Current treatments fail to prevent reinfection and remain expensive, limiting their use to developed countries, and the asymptomatic nature of acute infection can result in individuals not receiving treatment and unknowingly spreading HCV. A prophylactic vaccine is therefore needed to control this virus. Thirty years since the discovery of HCV, there have been major gains in understanding the molecular biology and elucidating the immunological mechanisms that underpin spontaneous viral clearance, aiding rational vaccine design. This review discusses the challenges facing HCV vaccine design and the most recent and promising candidates being investigated.

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Syntenin regulates hepatitis C virus sensitivity to neutralizing antibody by promoting E2 secretion through exosomes

Cited by 35 publications

References 45 publications

Mathematical modeling of hepatitis C RNA replication, exosome secretion and virus release

Mathematical modeling of hepatitis C RNA replication, exosome secretion and virus release

Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration

Hepatitis C Virus Vaccine: Challenges and Prospects

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