Use of the yellow fever virus vaccine strain 17D for the study of strategies for the treatment of yellow fever virus infections

Neyts, Johan; Meerbach, Astrid; McKenna, Paula; Clercq, Erik De

doi:10.1016/0166-3542(96)89697-5

Cited by 103 publications

(64 citation statements)

References 18 publications

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“…3). Consistent with this observation, it was previously reported that MTX inhibits the replication of another flavivirus, yellow fever virus, vaccine strain 17D (14).…”

Section: Mtx and Fudr Inhibit Denv Replicationsupporting

confidence: 74%

Flaviviruses Are Sensitive to Inhibition of Thymidine Synthesis Pathways

Fischer

Smith

Shum

et al. 2013

J Virol

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bDengue virus has emerged as a global health threat to over one-third of humankind. As a positive-strand RNA virus, dengue virus relies on the host cell metabolism for its translation, replication, and egress. Therefore, a better understanding of the host cell metabolic pathways required for dengue virus infection offers the opportunity to develop new approaches for therapeutic intervention. In a recently described screen of known drugs and bioactive molecules, we observed that methotrexate and floxuridine inhibited dengue virus infections at low micromolar concentrations. Here, we demonstrate that all serotypes of dengue virus, as well as West Nile virus, are highly sensitive to both methotrexate and floxuridine, whereas other RNA viruses (Sindbis virus and vesicular stomatitis virus) are not. Interestingly, flavivirus replication was restored by folinic acid, a thymidine precursor, in the presence of methotrexate and by thymidine in the presence of floxuridine, suggesting an unexpected role for thymidine in flavivirus replication. Since thymidine is not incorporated into RNA genomes, it is likely that increased thymidine production is indirectly involved in flavivirus replication. A possible mechanism is suggested by the finding that p53 inhibition restored dengue virus replication in the presence of floxuridine, consistent with thymidine-less stress triggering p53-mediated antiflavivirus effects in infected cells. Our data reveal thymidine synthesis pathways as new and unexpected therapeutic targets for antiflaviviral drug development. Dengue virus (DENV) poses a significant human health risk for approximately 40% of the world's population (http://www.who .int/mediacentre/factsheets/fs117/en/). DENV occurs as four serotypes, with increasing and widespread circulation of all serotypes considered a contributing factor for the rising incidence of dengue disease. A particularly severe complication is dengue hemorrhagic fever (DHF), which results in approximately 22,000 deaths annually and of which the incidence is currently on the rise (http://www .who.int/csr/disease/dengue/impact/en/index.html). However, even nonfatal, self-limiting DENV infection can result in a severe, painful disease that is also known as "break-bone fever." No vaccine or antiviral therapeutics are licensed to address DENV infections, and treatment is currently limited to supportive care.Many studies are ongoing with the hopes of identifying effective novel anti-DENV therapeutics and/or potential therapeutic targets. Several viral factors have been explored as therapeutic targets, including the viral protease, helicase, and RNA-dependent RNA polymerase (reviewed in reference 1). As an alternative to directly targeting viral proteins, it is conceivable to target host cell metabolic pathways that are required for viral replication. Flaviviruses, small RNA viruses that include DENV as well as West Nile virus (WNV), yellow fever virus, and Japanese encephalitis virus, are highly dependent on the host cell to provide support for viral entry, repl...

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“…3). Consistent with this observation, it was previously reported that MTX inhibits the replication of another flavivirus, yellow fever virus, vaccine strain 17D (14).…”

Section: Mtx and Fudr Inhibit Denv Replicationsupporting

confidence: 74%

Flaviviruses Are Sensitive to Inhibition of Thymidine Synthesis Pathways

Fischer

Smith

Shum

et al. 2013

J Virol

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“…[18][19][20]28 Neyts and De Clercq 18 reported the inhibitory effect of MMF and acyclovir on herpes virus in a murine model and in vitro. Birkeland et al 20 showed a reduced rate of primary or reactivation Epstein-Barr virus infection when MMF was administered with acyclovir to 208 kidney transplant recipients.…”

Section: Discussionmentioning

confidence: 99%

“…Mycophenolate mofetil (MMF) has proven antiviral activity both in vitro and in small animal models, apart from its proven immunosuppressive effect. [16][17][18][19][20] The aim of the present study is to examine the impact of MMF therapy in HCV-positive liver transplant recipients administered tacrolimus (TAC)-based immunosuppression. 21,22 One hundred six patients on this trial underwent LT for end-stage liver disease secondary to HCV infection.…”

mentioning

confidence: 99%

A prospective randomized trial of mycophenolate mofetil in liver transplant recipients with hepatitis C

Jain

2002

Liver Transplantation

129

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Hepatitis C is the most common indication for liver transplantation (LT) in the United States. Recurrence of hepatitis C virus (HCV) infection post-LT remains a problem for which there is no completely satisfactory treatment. The aim of the present study is to evaluate mycophenolate mofetil (MMF), which has both immunosuppressive and antiviral properties, to determine whether it is associated with a difference in the rate of HCV recurrence and also examine its impact on patient and graft survival. Between August 1995 and May 1998, a total of 106 patients who were HCV positive before LT were randomized to tacrolimus (

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“…Targeted reduction or point mutants of NTPase inhibit Toxoplasma gondii proliferation (31) and viral DNA replication (20). Small molecules designed to inhibit NTPase function may be promising antiviral drugs (3,8,34,38).…”

Section: Discussionmentioning

confidence: 99%

White Spot Syndrome Virus Proteins and Differentially Expressed Host Proteins Identified in Shrimp Epithelium by Shotgun Proteomics and Cleavable Isotope-Coded Affinity Tag

Lin

Lim

et al. 2007

J Virol

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Shrimp subcuticular epithelial cells are the initial and major targets of white spot syndrome virus (WSSV) infection. Proteomic studies of WSSV-infected subcuticular epithelium of Penaeus monodon were performed through two approaches, namely, subcellular fractionation coupled with shotgun proteomics to identify viral and host proteins and a quantitative time course proteomic analysis using cleavable isotope-coded affinity tags (cICATs) to identify differentially expressed cellular proteins. Peptides were analyzed by offline coupling of two-dimensional liquid chromatography with matrix-assisted laser desorption ionization-tandem time of flight mass spectrometry. We identified 27, 20, and 4 WSSV proteins from cytosolic, nuclear, and membrane fractions, respectively. Twentyeight unique WSSV proteins with high confidence (total ion confidence interval percentage [CI%], >95%) were observed, 11 of which are reported here for the first time, and 3 of these novel proteins were shown to be viral nonstructural proteins by Western blotting analysis. A first shrimp protein data set containing 1,999 peptides (ion score, >20) and 429 proteins (total ion score CI%, >95%) was constructed via shotgun proteomics. We also identified 10 down-regulated proteins and 2 up-regulated proteins from the shrimp epithelial lysate via cICAT analysis. This is the first comprehensive study of WSSV-infected epithelia by proteomics. The 11 novel viral proteins represent the latest addition to our knowledge of the WSSV proteome. Three proteomic data sets consisting of WSSV proteins, epithelial cellular proteins, and differentially expressed cellular proteins generated in the course of WSSV infection provide a new resource for further study of WSSV-shrimp interactions.White spot syndrome virus (WSSV) has been a catastrophic pathogen of cultured peneid shrimps since its first appearance in the early 1990s (32). The initial and major target of this virus is shrimp epithelia, including subcuticular, stomach, and gill epithelia. WSSV-infected epithelial cells show hypertrophied nuclei containing massive amounts of viruses (26). Genomic studies revealed that the virus consists of a double-stranded DNA of about 300 kbp with more than 180 predicted open reading frames (ORFs) (9,43,54). So far, the majority of proteins encoded by the predicted ORFs have not been detected, and functions of many of these presumptive proteins remain elusive. Information on virus-host interactions is therefore very limited.Proteomics has been demonstrated to be an important platform technology and has contributed to our understanding of virus-host interaction (4, 37). Shotgun two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) is a promising approach for high-throughput identification of proteins (21, 48). Cleavable isotope-coded affinity tags (cICATs) coupled with 2D-LC-MS/MS enable the quantitative pairwise comparison of protein expression levels in uninfected and infected cells (7,15). Previous proteomic studies on WSSV had identified more than 40 ...

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Use of the yellow fever virus vaccine strain 17D for the study of strategies for the treatment of yellow fever virus infections

Cited by 103 publications

References 18 publications

Flaviviruses Are Sensitive to Inhibition of Thymidine Synthesis Pathways

Flaviviruses Are Sensitive to Inhibition of Thymidine Synthesis Pathways

A prospective randomized trial of mycophenolate mofetil in liver transplant recipients with hepatitis C

White Spot Syndrome Virus Proteins and Differentially Expressed Host Proteins Identified in Shrimp Epithelium by Shotgun Proteomics and Cleavable Isotope-Coded Affinity Tag

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