Free fatty acids or high-concentration glucose enhances hepatitis A virus replication in association with a reduction in glucose-regulated protein 78 expression

Win, Nan Nwe; Nakamura, Masato; Nakamoto, Shingo; Okamoto, Hiroaki; Yokosuka, Osamu; Shirasawa, Hiroshi

doi:10.1016/j.bbrc.2016.12.080

Cited by 12 publications

(19 citation statements)

References 18 publications

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“…The results of the present study support the recent study (27) and indicate that GRP78 is an attractive target for controlling HAV infection. In conclusion, GRP78 may be an intracellular anti-HAV factor, and is a novel line of defense against HAV in hepatocytes.…”

Section: Methodssupporting

confidence: 92%

Glucose-regulated protein 78 is an antiviral against hepatitis A virus replication

Jiang

Haga

Sasaki

et al. 2017

Experimental and Therapeutic Medicine

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Infection with hepatitis A virus (HAV) is a major cause of acute hepatitis globally and it is important to identify the mechanisms of HAV replication. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum (ER) chaperone and serves a role in unfolded protein response pathways. Previous studies have demonstrated that GRP78 functions as an endogenous antiviral factor. In the present study, two loss-of-function studies using GRP78 were completed to elucidate the role of GRP78 in HAV infection. HAV replication was observed to be enhanced by deficient GRP78 although GRP78-deficiency also led to lower expression of ER stress molecules downstream of GRP78. Therefore, GRP78 appears to be a potential novel defensive molecule against HAV in hepatocytes.

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Section: Methodssupporting

confidence: 92%

Glucose-regulated protein 78 is an antiviral against hepatitis A virus replication

Jiang

Haga

Sasaki

et al. 2017

Experimental and Therapeutic Medicine

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“…23 High concentrations of glucose reportedly enhance HAV replication in vitro in association with a reduction in glucoseregulated protein 78 expression in human hepatocytes. 24 In contrast, the serum HAV-RNA levels were shown to be strongly correlated with the severity of acute hepatitis caused by HAV infection, 25 and severe hepatitis could develop especially in patients in whom the serum HAV-RNA levels have decreased rapidly through immune responses responsible for hepatitis provocation. 26 These observations have prompted us to evaluate the significance of diabetes mellitus as a factor in the deterioration of patient outcome among elderly patients with HAV infections.…”

Section: Discussionmentioning

confidence: 98%

“…reported that underlying diabetes mellitus was a significant factor associated with the aggravation of acute hepatitis in patients in India . High concentrations of glucose reportedly enhance HAV replication in vitro in association with a reduction in glucose‐regulated protein 78 expression in human hepatocytes . In contrast, the serum HAV‐RNA levels were shown to be strongly correlated with the severity of acute hepatitis caused by HAV infection, and severe hepatitis could develop especially in patients in whom the serum HAV‐RNA levels have decreased rapidly through immune responses responsible for hepatitis provocation .…”

Section: Discussionmentioning

confidence: 99%

Deteriorated outcome of recent patients with acute liver failure and late‐onset hepatic failure caused by infection with hepatitis A virus: A subanalysis of patients seen between 1998 and 2015 and enrolled in nationwide surveys in Japan

Nakazato

Nakayama

Uchida

et al. 2019

Hepatology Research

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Aim A nationwide survey of acute liver failure (ALF) and late‐onset hepatic failure (LOHF) has revealed that the outcomes of recent patients whose diseases were caused by infection with hepatitis A virus (HAV) have worsened, compared with those of previously reported patients. The factors associated with this deterioration were evaluated. Methods A total of 83 patients with HAV infection seen between 1998 and 2015 were enrolled. All the patients had a prothrombin time–international normalized ratio of 1.5 or more and hepatic encephalopathy of grade 2 or more severe. The demographic and clinical features of 45 patients seen prior to 2003 (cohort 1) and 38 patients seen during 2004 and thereafter (cohort 2) were compared. Results Three and four patients in cohort 1 and cohort 2, respectively, received liver transplantations; the survival rates among the remaining patients were 56% for cohort 2 and 79% for cohort 1 (P < 0.05). The mean age (±standard deviation) of the patients was higher in cohort 2 than in cohort 1 (58 ± 11 vs. 48 ± 13 years; P < 0.01). The percentages of patients with underlying metabolic diseases were 22% in cohort 1 and 61% in cohort 2 (P < 0.01). Diabetic mellitus was more common among deceased patients than among rescued patients (29% vs. 8%; P < 0.05) among patients who did not receive liver transplantations, and a multivariate analysis revealed that patient age and disease type were significantly and independently associated with the outcome. Conclusion The outcomes of recent patients with ALF or LOHF caused by HAV infection have recently worsened mainly because of an increase in underlying metabolic diseases as a consequence of aging.

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“…Among tyrosine kinase inhibitors identified by ViroTreat, dasatinib was previously described to inhibit MERS-CoV (5,19) and HIV-1 (70) replication in vitro; while erlotinib was shown to inhibit dengue(71), hepatitis C(72) and ebola (73) replication. The HSP90 inhibitors SNX-2112 and luminespib, as well as the sarco/endoplasmatic reticulum Ca 2+ ATPase inhibitor thapsigargin, all identified by ViroTreat as inverters of the SARS-CoV induced checkpoint, have been shown to inhibit herpes simplex (74), chikungunya(75), foot and mouth disease virus(76), respiratory syncytial virus(77), rhinovirus(78) and hepatitis A virus replication (79).…”

Section: Discussionmentioning

confidence: 99%

The Host Cell ViroCheckpoint: Identification and Pharmacologic Targeting of Novel Mechanistic Determinants of Coronavirus-Mediated Hijacked Cell States

Laise

Bosker

Sun

et al. 2020

Preprint

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Most antiviral agents are designed to target virus-specific proteins and mechanisms rather than the host cell proteins that are critically dysregulated following virus-mediated reprogramming of the host cell transcriptional state. To overcome these limitations, we propose that elucidation and pharmacologic targeting of host cell Master Regulator proteins-whose aberrant activities govern the reprogramed state of coronavirusinfected cells-presents unique opportunities to develop novel mechanism-based therapeutic approaches to antiviral therapy, either as monotherapy or as a complement to established treatments. Specifically, we propose that a small module of host cell Master Regulator proteins (ViroCheckpoint) is hijacked by the virus to support its efficient replication and release. Conventional methodologies are not well suited to elucidate these potentially targetable proteins. By using the VIPER network-based algorithm, we successfully interrogated 12h, 24h, and 48h signatures from Calu-3 lung adenocarcinoma cells infected with SARS-CoV, to elucidate the time-dependent reprogramming of host cells and associated Master Regulator proteins. We used the NYS CLIA-certified Darwin OncoTreat algorithm, with an existing database of RNASeq profiles following cell perturbation with 133 FDA-approved and 195 late-stage experimental compounds, to identify drugs capable of virtually abrogating the virus-induced Master Regulator signature. This approach to drug prioritization and repurposing can be trivially extended to other viral pathogens, including SARS-CoV-2, as soon as the relevant infection signature becomes available.

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Free fatty acids or high-concentration glucose enhances hepatitis A virus replication in association with a reduction in glucose-regulated protein 78 expression

Cited by 12 publications

References 18 publications

Glucose-regulated protein 78 is an antiviral against hepatitis A virus replication

Glucose-regulated protein 78 is an antiviral against hepatitis A virus replication

Deteriorated outcome of recent patients with acute liver failure and late‐onset hepatic failure caused by infection with hepatitis A virus: A subanalysis of patients seen between 1998 and 2015 and enrolled in nationwide surveys in Japan

The Host Cell ViroCheckpoint: Identification and Pharmacologic Targeting of Novel Mechanistic Determinants of Coronavirus-Mediated Hijacked Cell States

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