Comparative analysis of the L, M, and S RNA segments of Crimean-Congo haemorrhagic fever virus isolates from southern Africa

Goedhals, Dominique; Bester, Phillip Armand; Pawęska, Janusz T.; Swanepoel, Robert; Burt, Felicity J.

doi:10.1002/jmv.24079

Cited by 7 publications

(4 citation statements)

References 37 publications

(57 reference statements)

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“…As M segments, and therefore GPCs, are commonly exchanged between CCHFV strains [ 20 , 21 , 28 – 30 ], we assessed the compatibility between IbAr10200 replication machinery and mature glycoproteins from several pathogenic strains of CCHFV. To study the production of tecVLPs by the IbAr10200 replication machinery, GPCs from CCHFV strains Turkey, Oman, and Afg09 were expressed in the tecVLP system in place of IbAr10200 GPC.…”

Section: Resultsmentioning

confidence: 99%

Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles

et al. 2015

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Crimean-Congo hemorrhagic fever (CCHF) is an often lethal, acute inflammatory illness that affects a large geographic area. The disease is caused by infection with CCHF virus (CCHFV), a nairovirus from the Bunyaviridae family. Basic research on CCHFV has been severely hampered by biosafety requirements and lack of available strains and molecular tools. We report the development of a CCHF transcription- and entry-competent virus-like particle (tecVLP) system that can be used to study cell entry and viral transcription/replication over a broad dynamic range (~4 orders of magnitude). The tecVLPs are morphologically similar to authentic CCHFV. Incubation of immortalized and primary human cells with tecVLPs results in a strong reporter signal that is sensitive to treatment with neutralizing monoclonal antibodies and by small molecule inhibitors of CCHFV. We used glycoproteins and minigenomes from divergent CCHFV strains to generate tecVLPs, and in doing so, we identified a monoclonal antibody that can prevent cell entry of tecVLPs containing glycoproteins from 3 pathogenic CCHFV strains. In addition, our data suggest that different glycoprotein moieties confer different cellular entry efficiencies, and that glycoproteins from the commonly used strain IbAr10200 have up to 100-fold lower ability to enter primary human cells compared to glycoproteins from pathogenic CCHFV strains.

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Section: Resultsmentioning

confidence: 99%

Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles

et al. 2015

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“…NP has been investigated as a target for diagnostic proteins due to its immunogenicty, abundance and homology between isolates. However although there is less sequence homology in the M gene compared to the S gene encoding for NP, a significant amount of the diversity is located within the mucin-like region with less than 10% amino acid diversity determined for the remainder of the GP [ 24 ]. It is probable that epitopes inducing immunodominant and/or neutralising responses are more likely to be conserved between isolates and in the absence of detailed data regarding immunodominant epitopes in the GP it is appropriate to further define if there are conserved regions with possible roles in development of diagnostic tools and incorporation in vaccine design.…”

Section: Discussionmentioning

confidence: 99%

Epitope-mapping of the glycoprotein from Crimean-Congo hemorrhagic fever virus using a microarray approach

et al. 2018

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Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe acute human disease with lethal outcome. The knowledge about the immune response for this human health threat is highly limited. In this study, we have screened the glycoprotein of CCHFV for novel linear B-cell epitopic regions using a microarray approach. The peptide library consisted of 168 synthesized 20mer peptides with 10 amino acid overlap covering the entire glycoprotein. Using both pooled and individual human sera from survivors of CCHF disease in Turkey five peptide epitopes situated in the mucin-like region and GP 38 (G15-515) and GN G516-1037 region of the glycoprotein were identified as epitopes for a CCHF immune response. An epitope walk of the five peptides revealed a peptide sequence located in the GN region with high specificity and sensitivity. This peptide sequence, and a sequence downstream, reacted also against sera from survivors of CCHF disease in South Africa. The cross reactivity of these peptides with samples from a geographically distinct region where genetically diverse strains of the virus circulate, enabled the identification of unique peptide epitopes from the CCHF glycoprotein that could have application in development of diagnostic tools. In this study clinical samples from geographically distinct regions were used to identify conserved linear epitopic regions of the glycoprotein of CCHF.

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“…Most cases occur in summer, when adult Hyalomma ticks manifest peak questing activity. A high degree of genetic diversity and occurrence of natural reassortment events are observed between southern African isolates and Asian or west African isolates (Goedhals et al, 2015). Differential diagnosis is important, because another tick-borne disease, typhus (caused by Rickettsia conorii), is highly prevalent in southern Africa.…”

Section: South Africamentioning

confidence: 99%

Meeting report: First International Conference on Crimean-Congo hemorrhagic fever

et al. 2015

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Comparative analysis of the L, M, and S RNA segments of Crimean-Congo haemorrhagic fever virus isolates from southern Africa

Abstract: Crimean-Congo haemorrhagic fever virus (CCHFV) is a member of the Bunyaviridae family with a tripartite, negative sense RNA genome. This study used predictive software to analyse the L (large), M (medium) and S (small) segments of 14 southern African CCHFV

Cited by 7 publications

References 37 publications

Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles

Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles

Epitope-mapping of the glycoprotein from Crimean-Congo hemorrhagic fever virus using a microarray approach

Meeting report: First International Conference on Crimean-Congo hemorrhagic fever

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