scholarly journals Inhibition of Orbivirus Replication by Fluvastatin and Identification of the Key Elements of the Mevalonate Pathway Involved

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1437
Author(s):  
Fauziah Mohd Jaafar ◽  
Baptiste Monsion ◽  
Mourad Belhouchet ◽  
Peter P. C. Mertens ◽  
Houssam Attoui
Keyword(s):  
Mevalonate Pathway ◽  
African Swine Fever Virus ◽  
Plaque Assay ◽  
African Swine Fever ◽  
Mevalonic Acid ◽  
Antiviral Effect ◽  
Structural Protein ◽  
Mevalonic Acid Pathway ◽  
Acid Pathway ◽  
Coa Reductase

Statin derivatives can inhibit the replication of a range of viruses, including hepatitis C virus (HCV, Hepacivirus), dengue virus (Flavivirus), African swine fever virus (Asfarviridae) and poliovirus (Picornaviridae). We assess the antiviral effect of fluvastatin in cells infected with orbiviruses (bluetongue virus (BTV) and Great Island virus (GIV)). The synthesis of orbivirus outer-capsid protein VP2 (detected by confocal immunofluorescence imaging) was used to assess levels of virus replication, showing a reduction in fluvastatin-treated cells. A reduction in virus titres of ~1.7 log (98%) in fluvastatin-treated cells was detected by a plaque assay. We have previously identified a fourth non-structural protein (NS4) of BTV and GIV, showing that it interacts with lipid droplets in infected cells. Fluvastatin, which inhibits 3-hydroxy 3-methyl glutaryl CoA reductase in the mevalonic acid pathway, disrupts these NS4 interactions. These findings highlight the role of the lipid pathways in orbivirus replication and suggest a greater role for the membrane-enveloped orbivirus particles than previously recognised. Chemical intermediates of the mevalonic acid pathway were used to assess their potential to rescue orbivirus replication. Pre-treatment of IFNAR(−/−) mice with fluvastatin promoted their survival upon challenge with live BTV, although only limited protection was observed.

scholarly journals The effects of statins on the mevalonic acid pathway in recombinant yeast strains expressing human HMG-CoA reductase

2013 ◽  
Vol 13 (1) ◽  
pp. 68 ◽  
Author(s):  
Agata Maciejak ◽  
Agata Leszczynska ◽  
Ilona Warchol ◽  
Monika Gora ◽  
Joanna Kaminska ◽  
...  
Keyword(s):  
Mevalonic Acid ◽  
Recombinant Yeast ◽  
Hmg Coa Reductase ◽  
Yeast Strains ◽  
Mevalonic Acid Pathway ◽  
Acid Pathway ◽  
Coa Reductase ◽  
Recombinant Yeast Strains

scholarly journals Microbial biotransformation as a tool for drug development based on natural products from mevalonic acid pathway: A review

2015 ◽  
Vol 6 (1) ◽  
pp. 17-33 ◽  
Author(s):  
Mohamed-Elamir F. Hegazy ◽  
Tarik A. Mohamed ◽  
Abdelsamed I. ElShamy ◽  
Abou-El-Hamd H. Mohamed ◽  
Usama A. Mahalel ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Development ◽  
Mevalonic Acid ◽  
Mevalonic Acid Pathway ◽  
Acid Pathway

scholarly journals African Swine Fever Virus pB119L Protein Is a Flavin Adenine Dinucleotide-Linked Sulfhydryl Oxidase

2006 ◽  
Vol 80 (7) ◽  
pp. 3157-3166 ◽  
Author(s):  
Irene Rodríguez ◽  
Modesto Redrejo-Rodríguez ◽  
Javier M. Rodríguez ◽  
Alí Alejo ◽  
José Salas ◽  
...  
Keyword(s):  
Disulfide Bonds ◽  
Flavin Adenine Dinucleotide ◽  
Virus Assembly ◽  
Nonstructural Protein ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
Structural Protein ◽  
Sulfhydryl Oxidase ◽  
Infected Cells

ABSTRACT Protein pB119L of African swine fever virus belongs to the Erv1p/Alrp family of sulfhydryl oxidases and has been described as a late nonstructural protein required for correct virus assembly. To further our knowledge of the function of protein pB119L during the virus life cycle, we have investigated whether this protein possesses sulfhydryl oxidase activity, using a purified recombinant protein. We show that the purified protein contains bound flavin adenine dinucleotide and is capable of catalyzing the formation of disulfide bonds both in a protein substrate and in the small molecule dithiothreitol, the catalytic activity being comparable to that of the Erv1p protein. Furthermore, protein pB119L contains the cysteines of its active-site motif CXXC, predominantly in an oxidized state, and forms noncovalently bound dimers in infected cells. We also show in coimmunoprecipitation experiments that protein pB119L interacts with the viral protein pA151R, which contains a CXXC motif similar to that present in thioredoxins. Protein pA151R, in turn, was found to interact with the viral structural protein pE248R, which contains disulfide bridges and belongs to a class of myristoylated proteins related to vaccinia virus L1R, one of the substrates of the redox pathway encoded by this virus. These results suggest the existence in African swine fever virus of a system for the formation of disulfide bonds constituted at least by proteins pB119L and pA151R and identify protein pE248R as a possible final substrate of this pathway.

scholarly journals African Swine Fever Virus Structural Protein pE120R Is Essential for Virus Transport from Assembly Sites to Plasma Membrane but Not for Infectivity

2001 ◽  
Vol 75 (15) ◽  
pp. 6758-6768 ◽  
Author(s):  
Germán Andrés ◽  
Ramón Garcı́a-Escudero ◽  
Eladio Viñuela ◽  
Marı́a L. Salas ◽  
Javier M. Rodrı́guez
Keyword(s):  
Plasma Membrane ◽  
African Swine Fever Virus ◽  
Growth Curves ◽  
African Swine Fever ◽  
Fever Virus ◽  
Virus Yield ◽  
Virus Infectivity ◽  
Structural Protein ◽  
Virus Growth ◽  
Extracellular Virus

ABSTRACT This report examines the role of African swine fever virus (ASFV) structural protein pE120R in virus replication. Immunoelectron microscopy revealed that protein pE120R localizes at the surface of the intracellular virions. Consistent with this, coimmunoprecipitation assays showed that protein pE120R binds to the major capsid protein p72. Moreover, it was found that, in cells infected with an ASFV recombinant that inducibly expresses protein p72, the incorporation of pE120R into the virus particle is dependent on p72 expression. Protein pE120R was also studied using an ASFV recombinant in which E120R gene expression is regulated by the Escherichia coli lacrepressor-operator system. In the absence of inducer, pE120R expression was reduced about 100-fold compared to that obtained with the parental virus or the recombinant virus grown under permissive conditions. One-step virus growth curves showed that, under conditions that repress pE120R expression, the titer of intracellular progeny was similar to the total virus yield obtained under permissive conditions, whereas the extracellular virus yield was about 100-fold lower than in control infections. Immunofluorescence and electron microscopy demonstrated that, under restrictive conditions, intracellular mature virions are properly assembled but remain confined to the replication areas. Altogether, these results indicate that pE120R is necessary for virus dissemination but not for virus infectivity. The data also suggest that protein pE120R might be involved in the microtubule-mediated transport of ASFV particles from the viral factories to the plasma membrane.

scholarly journals Peroxisomal Localization of Arabidopsis Isopentenyl Diphosphate Isomerases Suggests That Part of the Plant Isoprenoid Mevalonic Acid Pathway Is Compartmentalized to Peroxisomes

2008 ◽  
Vol 148 (3) ◽  
pp. 1219-1228 ◽  
Author(s):  
Maya Sapir-Mir ◽  
Anahit Mett ◽  
Eduard Belausov ◽  
Shira Tal-Meshulam ◽  
Ahuva Frydman ◽  
...  
Keyword(s):  
Mevalonic Acid ◽  
Isopentenyl Diphosphate ◽  
Mevalonic Acid Pathway ◽  
Acid Pathway

scholarly journals Characterization of the African Swine Fever Virus Structural Protein p14.5: A DNA Binding Protein

Virology ◽  
1997 ◽  
Vol 229 (1) ◽  
pp. 201-211 ◽  
Author(s):  
Luisa Martinez-Pomares ◽  
Carmen Simon-Mateo ◽  
Carlos Lopez-Otin ◽  
Eladio Viñuela
Keyword(s):  
Dna Binding ◽  
African Swine Fever Virus ◽  
Binding Protein ◽  
African Swine Fever ◽  
Dna Binding Protein ◽  
Fever Virus ◽  
Structural Protein

scholarly journals Production and application of mouse monoclonal antibodies targeting linear epitopes in pB602L of African swine fever virus

2022 ◽  
Author(s):  
Pengfei Wang ◽  
Chunguo Liu ◽  
Shida Wang ◽  
Lili Wen ◽  
Zhibin Shi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Immunohistochemical Staining ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Diagnostic Tools ◽  
Hemorrhagic Disease ◽  
Structural Protein ◽  
Linear Epitopes ◽  
Group 2 ◽  
Basic And Applied Research

AbstractAfrican swine fever (ASF) is an acute hemorrhagic disease of domestic pigs. The causative agent of ASF, ASF virus (ASFV), is a double-stranded DNA virus, the sole member in the family Asfarviridae. The non-structural protein pB602L of ASFV is a molecular chaperone of the major capsid protein p72 and plays a key role in icosahedral capsid assembly. This protein is antigenic and is a target for developing diagnostic tools for ASF. To generate monoclonal antibodies (mAbs) against pB602L, a prokaryotically expressed recombinant pB602L protein was produced, purified, and used as an antigen to immunize mice. A total of eight mouse mAbs were obtained, and their binding epitopes were screened by Western blot using an overlapping set of polypeptides from pB602L. Three linear epitopes were identified and designated epitope 1 (366ANRERYNY373), epitope 2 (415GPDAPGLSI423), and epitope 3 (498EMLNVPDD505). Based on the epitope recognized, the eight mAbs were placed into three groups: group 1 (B2A1, B2F1, and B2D10), group 2 (B2H10, B2B2, B2D8, and B2A3), and group 3 (B2E12). The mAbs B2A1, B2H10, and B2E12, each representing one of the groups, were used to detect pB602L in ASFV-infected porcine alveolar macrophages (PAMs) and pig tissues, using an indirect fluorescence assay (IFA) and immunohistochemical staining, respectively. The results showed that pB602L was detectable with all three mAbs in immunohistochemical staining, but only B2H10 was suitable for detecting the proteins in ASFV-infected PAMs by IFA. In summary, we developed eight anti-pB602L mouse mAbs recognizing three linear epitopes in the protein, which can be used as reagents for basic and applied research on ASFV.

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