Analysis of Conserved, Computationally Predicted Epitope Regions for VP5 and VP7 Across three Orbiviruses

Russell, Bonnie L.; Parbhoo, Nishal; Gildenhuys, Samantha

doi:10.1177/1177932218755348

Cited by 12 publications

(7 citation statements)

References 132 publications

(107 reference statements)

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“…Based on the molecular interaction patterns, the complex of mouse vaccine and TLR3 was found to have the second highest number of hydrogen bonds after mouse vaccine-TLR4 complex and 276 non-bonded interactions. The outcome of molecular docking is consistent with the docking results of the previous studies (Bhattacharya and Roy 2008, Sun, Sun et al 2014, Russell, Parbhoo et al 2018.…”

Section: Molecular Dockingsupporting

confidence: 89%

Immuno-informatics Study Identifies Conserved T Cell Epitopes in Non-structural Proteins of Bluetongue Virus Serotypes: Formulation of Computationally Optimized Next-Generation Broad-spectrum Multiepitope Vaccine

Kolla,

Dutt,

Kumar

et al. 2023

Preprint

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Bluetongue (BT) is a significant arboviral disease affecting sheep, cattle, goats, and wild ruminants, posing serious economic challenges to livestock industry. Control efforts have been hampered by the existence of over 32 distinct BT virus (BTV) serotypes and the absence of broad-spectrum vaccines. Some key non-structural proteins of BTV, including NS1, NS2, and NS3, exhibit notable amino acid sequence conservation. Our findings reveal that mouse MHC class I (MHC-I) CD8+ T cell epitopes are highly conserved in NS1 and NS3, while MHC-II epitopes are prevalent in all the three non-structural NS 1-3 proteins. Similarly, both class I and II Bovine Leukocyte antigen-restricted CD8+ and CD4+ T cell epitopes are conserved within NS1, NS2, and NS3 proteins. To constructin silicobroad-spectrum vaccine, we subsequently screened these conserved epitopes based on antigenicity, allergenicity, toxicity, and solubility. Modeling and Refinement of the 3D structure models of vaccine constructs were achieved using protein modeling web servers. Our analysis revealed promising epitopes that exhibit strong binding affinities with low energies against two TLR receptors (TLR3 and TLR4). To ensure atomic-level stability, we evaluated the docking complexes of epitopes and receptors through all-atom molecular dynamics simulations (MDS). Encouragingly, our 100 nanoseconds MDS showed stable complexes with minimal RMSF values. Our study offers valuable insights into these conserved T cell epitopes as promising candidates for a broad-spectrum BT vaccine. We therefore encourage for their evaluation in animal models and natural hosts to assess their immunogenicity, safety, and efficacy for field use in the livestock.

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Section: Molecular Dockingsupporting

confidence: 89%

Immuno-informatics Study Identifies Conserved T Cell Epitopes in Non-structural Proteins of Bluetongue Virus Serotypes: Formulation of Computationally Optimized Next-Generation Broad-spectrum Multiepitope Vaccine

Kolla,

Dutt,

Kumar

et al. 2023

Preprint

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“…It is known that certain immunogenic epitopes of BTV and EHDV are highly conserved and cross-reactivity occurs with BTV VP7 mAbs [ 49 ]. Although VP7 is highly conserved within the BTV species, with up to 90% amino acid identity, significant variation can still be found [ 50 ]. The rabbit polyclonal antibody used in our study did not cross-react with either the Australian or the South African reference BTV-15 isolates ( Table 2 ), which is consistent with an earlier finding that mAbs raised against BTV-1 and BTV-16 failed to detect BTV-15 [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Bluetongue Virus (BTV) Antibodies for the Immunohistochemical Detection of BTV and Other Orbiviruses

et al. 2020

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The detection of bluetongue virus (BTV) antigens in formalin-fixed tissues has been challenging; therefore, only a limited number of studies on suitable immunohistochemical approaches have been reported. This study details the successful application of antibodies for the immunohistochemical detection of BTV in BSR variant baby hamster kidney cells (BHK-BSR) and infected sheep lungs that were formalin-fixed and paraffin-embedded (FFPE). BTV reactive antibodies raised against non-structural (NS) proteins 1, 2, and 3/3a and viral structural protein 7 (VP7) were first evaluated on FFPE BTV-infected cell pellets for their ability to detect BTV serotype 1 (BTV-1). Antibodies that were successful in immunolabelling BTV-1 infected cell pellets were further tested, using similar methods, to determine their broader immunoreactivity against a diverse range of BTV and other orbiviruses. Antibodies specific for NS1, NS2, and NS3/3a were able to detect all BTV isolates tested, and the VP7 antibody cross-reacted with all BTV isolates, except BTV-15. The NS1 antibodies were BTV serogroup-specific, while the NS2, NS3/3a, and VP7 antibodies demonstrated immunologic cross-reactivity to related orbiviruses. These antibodies also detected viral antigens in BTV-3 infected sheep lung. This study demonstrates the utility of FFPE-infected cell pellets for the development and validation of BTV immunohistochemistry.

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“…Targeted and rational design of EHDVs using the reverse genetics system may be further aided by methods such as structural modeling and epitope prediction. In a recent comparison of orbivirus sequences, consensus sequences for the VP5 and VP7 proteins of EHDV, BTV, and AHSV were obtained, and homology models were constructed to fill in knowledge gaps regarding the structure of EHDV proteins [88]. Subsequent computational analyses identified and mapped potential linear and discontinuous epitopes in these structural proteins of the inner and outer capsid proteins.…”

Section: Molecular Vaccine and Diagnostic Toolsmentioning

confidence: 99%

Perspectives on the Changing Landscape of Epizootic Hemorrhagic Disease Virus Control

Noronha

Cohnstaedt

Richt

et al. 2021

Viruses

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Epizootic hemorrhagic disease (EHD) is an insect-transmitted viral disease of wild and domestic ruminants. It was first described following a 1955 epizootic in North American white-tailed deer (Odocoileus virginianus), a species which is highly susceptible to the causative agent of EHD, epizootic hemorrhagic disease virus (EHDV). EHDV has been detected globally across tropical and temperate regions, largely corresponding to the presence of Culicoides spp. biting midges which transmit the virus between ruminant hosts. It regularly causes high morbidity and mortality in wild and captive deer populations in endemic areas during epizootics. Although cattle historically have been less susceptible to EHDV, reports of clinical disease in cattle have increased in the past two decades. There is a pressing need to identify new methods to prevent and mitigate outbreaks and reduce the considerable impacts of EHDV on livestock and wildlife. This review discusses recent research advancements towards the control of EHDV, including the development of new investigative tools and progress in basic and applied research focused on virus detection, disease mitigation, and vector control. The potential impacts and implications of these advancements on EHD management are also discussed.

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Analysis of Conserved, Computationally Predicted Epitope Regions for VP5 and VP7 Across three Orbiviruses

Cited by 12 publications

References 132 publications

Immuno-informatics Study Identifies Conserved T Cell Epitopes in Non-structural Proteins of Bluetongue Virus Serotypes: Formulation of Computationally Optimized Next-Generation Broad-spectrum Multiepitope Vaccine

Immuno-informatics Study Identifies Conserved T Cell Epitopes in Non-structural Proteins of Bluetongue Virus Serotypes: Formulation of Computationally Optimized Next-Generation Broad-spectrum Multiepitope Vaccine

Evaluation of Bluetongue Virus (BTV) Antibodies for the Immunohistochemical Detection of BTV and Other Orbiviruses

Perspectives on the Changing Landscape of Epizootic Hemorrhagic Disease Virus Control

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