scholarly journals Sheep and Cattle Are Not Susceptible to Experimental Inoculation with Hazara Orthonairovirus, a Tick-Borne Arbovirus Closely Related to CCHFV

2020 ◽  
Vol 8 (12) ◽  
pp. 1927
Author(s):  
Julia Hartlaub ◽  
Felicitas von Arnim ◽  
Christine Fast ◽  
Maryna Somova ◽  
Ali Mirazimi ◽  
...  
Keyword(s):  
Hemorrhagic Fever ◽  
Field Studies ◽  
Crimean Congo Hemorrhagic Fever ◽  
Diagnostic Problems ◽  
Experimental Inoculation ◽  
Natural Hosts ◽  
Biosafety Level

Hazara orthonairovirus (HAZV) is a tick-borne arbovirus closely related to Crimean–Congo hemorrhagic fever orthonairovirus (CCHFV). Whereas CCHFV is a biosafety level (BSL) 4 agent, HAZV is classified as BSL 2, as it is not known to cause any disease in humans. Belonging to the same serogroup as CCHFV, HAZV might act as a model which can provide a better understanding of this important zoonosis. Furthermore, the serological relatedness may cause diagnostic problems if antibodies against HAZV interfere with current CCHFV serological assays. Therefore, sheep and cattle—important natural hosts for CCHFV—were experimentally infected with HAZV to prove their susceptibility and evaluate potential antibody cross-reactivities. According to this study, neither sheep nor cattle are susceptible to experimental HAZV infections. Consequently, the HAZV infection in ruminants is clearly distinct from CCHFV infections. Sera of immunized animals weakly cross-reacted between HAZV and CCHFV in immunofluorescence and immunoblot assays, but not in commercial CCHFV ELISAs commonly used for field studies.

scholarly journals Development of a novel recombinant ELISA for the detection of Crimean-Congo hemorrhagic fever virus IgG antibodies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sultan Gülce-İz ◽  
Nazif Elaldı ◽  
Hüseyin Can ◽  
Esra Atalay Şahar ◽  
Muhammet Karakavuk ◽  
...  
Keyword(s):  
Hemorrhagic Fever ◽  
Field Studies ◽  
Fever Virus ◽  
Igg Antibodies ◽  
Serological Screening ◽  
Crimean Congo Hemorrhagic Fever ◽  
E Coli ◽  
Hemorrhagic Fever Virus ◽  
And Control ◽  
Recombinant Nucleocapsid Protein

AbstractCrimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral infection caused by Crimean-Congo hemorrhagic fever virus (CCHFV). Serological screening of CCHF is important and current ELISA use antigens prepared from virus which is expensive due to requirement of high bio-containment facilities. In this study, we aimed to develop a new recombinant ELISA. For this purpose, CCHFV genome were expressed as 13 proteins in E. coli and among them abundantly purified recombinant Nucleocapsid protein (rNP) and Mucin-like variable domain (rMLD) were used as antigen in ELISA (Rec-ELISA). Rec-ELISA using rNP, rMLD and a combination of both (rNP/rMLD) were probed with acute (n = 64; collected between days 1 and 7 after onset of symptoms), convalescent (n = 35; collected 8 days after onset of symptoms), consecutive sera (n = 25) of confirmed CCHF cases and control sera (n = 43). The sensitivity and specificity of Rec-ELISA using rNP/rMLD were 73% and 98% in acute cases and 97% and 98% in convalescent cases. The median interquartile absorbance value to discriminate the acute and convalescent phases of CCHF was significantly higher with ELISA using rNP/rMLD (P < 0.0001) compared to rNP (P > 0.05) and rMLD (P = 0.001). These results indicate that the Rec-ELISA using rNP/rMLD may be very useful to diagnose convalescent CCHF cases especially in field studies.

scholarly journals A Virus-Like Particle System Identifies the Endonuclease Domain of Crimean-Congo Hemorrhagic Fever Virus

2015 ◽  
Vol 89 (11) ◽  
pp. 5957-5967 ◽  
Author(s):  
Stephanie Devignot ◽  
Eric Bergeron ◽  
Stuart Nichol ◽  
Ali Mirazimi ◽  
Friedemann Weber
Keyword(s):  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Particle Assembly ◽  
Content Type ◽  
Virus Like Particles ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Virus Like Particle ◽  
Endonuclease Domain ◽  
Biosafety Level

ABSTRACTCrimean-Congo hemorrhagic fever virus(CCHFV; genusNairovirus) is an extremely pathogenic member of theBunyaviridaefamily. Since handling of the virus requires a biosafety level 4 (BSL-4) facility, little is known about pathomechanisms and host interactions. Here, we describe the establishment of a transcriptionally competent virus-like particle (tc-VLP) system for CCHFV. Recombinant polymerase (L), nucleocapsid protein (N) and a reporter minigenome expressed in human HuH-7 cells resulted in formation of transcriptionally active nucleocapsids that could be packaged by coexpressed CCHFV glycoproteins into tc-VLPs. The tc-VLPs resembled authentic virus particles in their protein composition and neutralization sensitivity to anti-CCHFV antibodies and could recapitulate all steps of the viral replication cycle. Particle attachment, entry, and primary transcription were modeled by infection of naive cells. The subsequent steps of genome replication, secondary transcription, and particle assembly and release can be obtained upon passaging the tc-VLPs on cells expressing CCHFV structural proteins. The utility of the VLP system was demonstrated by showing that the endonuclease domain of L is located around amino acid D693, as was predictedin silicoby B. Morin et al. (PLoS Pathog 6:e1001038, 2010,http://dx.doi.org/10.1371/journal.ppat.1001038). The tc-VLP system will greatly facilitate studies and diagnostics of CCHFV under non-BSL-4 conditions.IMPORTANCECrimean-Congo hemorrhagic fever virus (CCHFV) is an extremely virulent pathogen of humans. Since the virus can be handled only at the highest biosafety level, research is restricted to a few specialized laboratories. We developed a plasmid-based system to produce virus-like particles with the ability to infect cells and transcribe a reporter genome. Due to the absence of viral genes, the virus-like particles are unable to spread or cause disease, thus allowing study of aspects of CCHFV biology under relaxed biosafety conditions.

scholarly journals Crimean-Congo Hemorrhagic Fever Virus: Current Advances and Future Prospects of Antiviral Strategies

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1195
Author(s):  
Shiyu Dai ◽  
Fei Deng ◽  
Hualin Wang ◽  
Yunjia Ning
Keyword(s):  
Treatment Options ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Transmission Risk ◽  
High Morbidity ◽  
Tick Bites ◽  
Future Directions ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Biosafety Level

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widespread, tick-borne pathogen that causes Crimean-Congo hemorrhagic fever (CCHF) with high morbidity and mortality. CCHFV is transmitted to humans through tick bites or direct contact with patients or infected animals with viremia. Currently, climate change and globalization have increased the transmission risk of this biosafety level (BSL)-4 virus. The treatment options of CCHFV infection remain limited and there is no FDA-approved vaccine or specific antivirals, which urges the identification of potential therapeutic targets and the design of CCHF therapies with greater effort. In this article, we discuss the current progress and some future directions in the development of antiviral strategies against CCHFV.

scholarly journals Immunoglobulin-like Domain of HsFcμR as a Capture Molecule for Detection of Crimean-Congo Hemorrhagic Fever Virus- and Zika Virus-Specific IgM Antibodies

2019 ◽  
Vol 65 (3) ◽  
pp. 451-461 ◽  
Author(s):  
Anne Rackow ◽  
Christa Ehmen ◽  
Ronald von Possel ◽  
Raquel Medialdea-Carrera ◽  
David Brown ◽  
...  
Keyword(s):  
Zika Virus ◽  
Specific Binding ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Size Exclusion ◽  
Animal Origin ◽  
Serum Samples ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Igm Antibodies

Abstract BACKGROUND The cellular surface molecule HsTOSO/FAIM3/HsFcμR has been identified as an IgM-specific Fc receptor expressed on lymphocytes. Here, we show that its extracellular immunoglobulin-like domain (HsFcμR-Igl) specifically binds to IgM/antigen immune complexes (ICs) and exploit this property for the development of novel detection systems for IgM antibodies directed against Crimean-Congo hemorrhagic fever virus (CCHFV) and Zika virus (ZIKV). METHODS His-tagged HsFcμR-Igl was expressed in Escherichia coli and purified by affinity chromatography, oxidative refolding, and size-exclusion chromatography. Specific binding of HsFcμR-Igl to IgM/antigen ICs was confirmed, and 2 prototypic ELISAs for the detection of anti-CCHFV and anti-ZIKV IgM antibodies were developed. Thereby, patient sera and virus-specific recombinant antigens directly labeled with horseradish peroxidase (HRP) were coincubated on HsFcμR-Igl-coated ELISA plates. Bound ICs were quantified by measuring turnover of a chromogenic HRP substrate. RESULTS Assay validation was performed using paired serum samples from 15 Kosovar patients with a PCR-confirmed CCHFV infection and 28 Brazilian patients with a PCR-confirmed ZIKV infection, along with a panel of a priori CCHFV/ZIKV-IgM-negative serum samples. Both ELISAs were highly reproducible. Sensitivity and specificity were comparable with or even exceeded in-house gold standard testing and commercial kits. Furthermore, latex beads coated with HsFcμR-Igl aggregated upon coincubation with an IgM-positive serum and HRP-labeled antigen but not with either component alone, revealing a potential for use of HsFcμR-Igl as a capture molecule in aggregation-based rapid tests. CONCLUSIONS Recombinant HsFcμR-Igl is a versatile capture molecule for IgM/antigen ICs of human and animal origin and can be applied for the development of both plate- and bead-based serological tests.

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