Inhibition of Crimean-Congo Hemorrhagic Fever Viral Infectivity Yields in Vitro by Ribavirin

1989 ◽  
Vol 41 (5) ◽  
pp. 581-585 ◽  
Author(s):  
Douglas M. Watts ◽  
Denise Nash ◽  
Michael A. Ussery ◽  
Clarence J. Peters
Keyword(s):  
Hemorrhagic Fever ◽  
Viral Infectivity ◽  
Crimean Congo Hemorrhagic Fever

Hepatocyte pathway alterations in response to in vitro Crimean Congo hemorrhagic fever virus infection

2014 ◽  
Vol 179 ◽  
pp. 187-203 ◽  
Author(s):  
Christophe Fraisier ◽  
Raquel Rodrigues ◽  
Vinh Vu Hai ◽  
Maya Belghazi ◽  
Stéphanie Bourdon ◽  
...  
Keyword(s):  
Virus Infection ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus

scholarly journals Small interfering RNAs are highly effective inhibitors regarding Crimean-Congo hemorrhagic fever virus replication in vitro

2020 ◽  
Author(s):  
Fanni Földes ◽  
Mónika Madai ◽  
Henrietta Papp ◽  
Gábor Kemenesi ◽  
Brigitta Zana ◽  
...  
Keyword(s):  
Rna Interference ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
World Health ◽  
Dependent Manner ◽  
Small Interfering Rnas ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Antiviral Therapies

AbstractCrimean-Congo hemorrhagic fever virus (CCHFV) is one of the prioritized diseases of World Health Organization, considering its potential to create a public health emergency and more importantly, the absence of efficacious drugs and/or vaccines regarding treatment. The highly lethal nature characteristic to CCHFV restricts research to BSL-4 laboratories, which complicates effective research and developmental strategies. In consideration of antiviral therapies, RNA interference can be used to suppress viral replication by targeting viral genes. RNA interference uses small interfering RNAs (siRNAs) to silence genes. The aim of our study was to design siRNAs that inhibit CCHFV replication and can serve as a basis for further antiviral therapies. A549 cells were infected with CCHFV after transfection with the siRNAs. Following 72 hours, nucleic acid from the supernatant was extracted for Droplet Digital PCR analysis. Among the investigated siRNAs we identified four effective candidates against all three segments of CCHF genome: one for the S and M segments, whilst two for the L segment. Consequently, blocking any segment of CCHFV leads to changes in the virus copy number that indicates an antiviral effect of the siRNAs in vitro. The most active siRNAs were demonstrated a specific inhibitory effect against CCHFV in a dose-dependent manner. In summary, we demonstrated the ability of specific siRNAs to inhibit CCHFV replication in vitro. This promising result can be used in future anti-CCHFV therapy developments.

scholarly journals Antagonistic Antiviral Activity between IFN-Lambda and IFN-Alpha against Lethal Crimean-Congo Hemorrhagic Fever Virus In Vitro

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0116816 ◽  
Author(s):  
Licia Bordi ◽  
Eleonora Lalle ◽  
Claudia Caglioti ◽  
Damiano Travaglini ◽  
Daniele Lapa ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Ifn Alpha ◽  
Ifn Lambda

scholarly journals Small Interfering RNAs Are Highly Effective Inhibitors of Crimean-Congo Hemorrhagic Fever Virus Replication In Vitro

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5771
Author(s):  
Fanni Földes ◽  
Mónika Madai ◽  
Henrietta Papp ◽  
Gábor Kemenesi ◽  
Brigitta Zana ◽  
...  
Keyword(s):  
Rna Interference ◽  
A549 Cells ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
World Health ◽  
Small Interfering Rnas ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Antiviral Therapies

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the prioritized diseases of the World Health Organization, considering its potential to create a public health emergency and, more importantly, the absence of efficacious drugs and/or vaccines for treatment. The highly pathogenic characteristic of CCHFV restricts research to BSL-4 laboratories, which complicates effective research and developmental strategies. In consideration of antiviral therapies, RNA interference can be used to suppress viral replication by targeting viral genes. RNA interference uses small interfering RNAs (siRNAs) to silence genes. The aim of our study was to design and test siRNAs in vitro that inhibit CCHFV replication and can serve as a basis for further antiviral therapies. A549 cells were infected with CCHFV after transfection with the siRNAs. Following 72 h, nucleic acid from the supernatant was extracted for RT Droplet Digital PCR analysis. Among the investigated siRNAs we identified effective candidates against all three segments of the CCHF genome. Consequently, blocking any segment of CCHFV leads to changes in the virus copy number that indicates an antiviral effect of the siRNAs. In summary, we demonstrated the ability of specific siRNAs to inhibit CCHFV replication in vitro. This promising result can be integrated into future anti-CCHFV therapy developments.

scholarly journals The Crimean-Congo Hemorrhagic Fever Virus NSm Protein Is Dispensable for Growth In Vitro and Disease in Ifnar-/- Mice

2020 ◽  
Vol 8 (5) ◽  
pp. 775 ◽  
Author(s):  
Stephen R. Welch ◽  
Florine E. M. Scholte ◽  
Jessica R. Spengler ◽  
Jana M. Ritter ◽  
JoAnn D. Coleman-McCray ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Structural Proteins ◽  
Glycoprotein Precursor ◽  
Crimean Congo Hemorrhagic Fever ◽  
Virus Attachment ◽  
Hemorrhagic Fever Virus ◽  
Endoproteolytic Cleavage

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tri-segmented, tick-borne nairovirus that causes disease of ranging severity in humans. The CCHFV M segment encodes a complex glycoprotein precursor (GPC) that undergoes extensive endoproteolytic cleavage, giving rise to two structural proteins (Gn and Gc) required for virus attachment and entry, and to multiple non-structural proteins (NSm, GP160, GP85, and GP38). The functions of these non-structural proteins remain largely unclear. Here, we investigate the role of NSm during infection by generating a recombinant CCHFV lacking the complete NSm domain (10200∆NSm) and observing CCHFV ∆NSm replication in cell lines and pathogenicity in Ifnar-/- mice. Our data demonstrate that the NSm domain is dispensable for viral replication in vitro, and, despite the delayed onset of clinical signs, CCHFV lacking this domain caused severe or lethal disease in infected mice.

scholarly journals Differential Growth Characteristics of Crimean-Congo Hemorrhagic Fever Virus in Kidney Cells of Human and Bovine Origin

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 685
Author(s):  
Katalin Földes ◽  
Touraj Aligholipour Farzani ◽  
Koray Ergünay ◽  
Aykut Ozkul
Keyword(s):  
Cell Lines ◽  
Human Kidney ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Kidney Cells ◽  
Bovine Kidney ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
The Impact

Crimean-Congo hemorrhagic fever virus (CCHFV) causes a lethal tick-borne zoonotic disease with severe clinical manifestation in humans but does not produce symptomatic disease in wild or domestic animals. The factors contributing to differential outcomes of infection between species are not yet understood. Since CCHFV is known to have tropism to kidney tissue and cattle play an important role as an amplifying host for CCHFV, in this study, we assessed in vitro cell susceptibility to CCHFV infection in immortalized and primary kidney and adrenal gland cell lines of human and bovine origin. Based on our indirect fluorescent focus assay (IFFA), we suggest a cell-to-cell CCHF viral spread process in bovine kidney cells but not in human cells. Over the course of seven days post-infection (dpi), infected bovine kidney cells are found in restricted islet-like areas. In contrast, three dpi infected human kidney or adrenal cells were noted in areas distant from one another yet progressed to up to 100% infection of the monolayer. Pronounced CCHFV replication, measured by quantitative real-time RT-PCR (qRT-PCR) of both intra- and extracellular viral RNA, was documented only in human kidney cells, supporting restrictive infection in cells of bovine origin. To further investigate the differences, lactate dehydrogenase activity and cytopathic effects were measured at different time points in all mentioned cells. In vitro assays indicated that CCHFV infection affects human and bovine kidney cells differently, where human cell lines seem to be markedly permissive. This is the initial reporting of CCHFV susceptibility and replication patterns in bovine cells and the first report to compare human and animal cell permissiveness in vitro. Further investigations will help to understand the impact of different cell types of various origins on the virus–host interaction.

scholarly journals Crimean-Congo Hemorrhagic Fever Virus Glycoprotein Proteolytic Processing by Subtilase SKI-1

2003 ◽  
Vol 77 (16) ◽  
pp. 8640-8649 ◽  
Author(s):  
Martin J. Vincent ◽  
Angela J. Sanchez ◽  
Bobbie R. Erickson ◽  
Ajoy Basak ◽  
Michel Chretien ◽  
...  
Keyword(s):  
Hemorrhagic Fever ◽  
Proteolytic Processing ◽  
Lassa Virus ◽  
Glycoprotein Precursor ◽  
Virus Family ◽  
Apparent Lack ◽  
Crimean Congo Hemorrhagic Fever ◽  
Cchf Virus ◽  
Processing Site

ABSTRACT Crimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne member of the genus Nairovirus, family Bunyaviridae. The mature virus glycoproteins, Gn and Gc (previously referred to as G2 and G1), are generated by proteolytic cleavage from precursor proteins. The amino termini of Gn and Gc are immediately preceded by tetrapeptides RRLL and RKPL, respectively, leading to the hypothesis that SKI-1 or related proteases may be involved (A. J. Sanchez, M. J. Vincent, and S. T. Nichol, J. Virol. 76:7263-7275, 2002). In vitro peptide cleavage data show that an RRLL peptide representing the Gn processing site is efficiently cleaved by SKI-1 protease, whereas an RKPL peptide representing the Gc processing site is cleaved at negligible levels. The efficient cleavage of RRLL peptide is consistent with the known recognition sequences of SKI-1, including the sequence determinants involved in the cleavage of the Lassa virus (family Arenaviridae) glycoprotein precursor. These in vitro findings were confirmed by expression of wild-type or mutant CCHF virus glycoproteins in CHO cells engineered to express functional or nonfunctional SKI-1. Gn processing was found to be dependent on functional SKI-1, whereas Gc processing was not. Gn processing occurred in the endoplasmic reticulum-cis Golgi compartments and was dependent on an R at the −4 position within the RRLL recognition motif, consistent with the known cleavage properties of SKI-1. Comparison of SKI-1 cleavage efficiency between peptides representing Lassa virus GP2 and CCHF virus Gn cleavage sites suggests that amino acids flanking the RRLL may modulate the efficiency. The apparent lack of SKI-1 cleavage at the CCHF virus Gc RKPL site indicates that related proteases, other than SKI-1, are likely to be involved in the processing at this site and identical or similar sites utilized in several New World arenaviruses.

scholarly journals Development of a Novel Multi-Epitope Vaccine Against Crimean-Congo Hemorrhagic Fever Virus: An Integrated Reverse Vaccinology, Vaccine Informatics and Biophysics Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Muhammad Tahir Ul Qamar ◽  
Saba Ismail ◽  
Sajjad Ahmad ◽  
Muhammad Usman Mirza ◽  
Sumra Wajid Abbasi ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Experimental Analysis ◽  
3D Structure ◽  
Hemorrhagic Fever ◽  
Viral Disease ◽  
Antigenic Determinants ◽  
Epitope Vaccine ◽  
Crimean Congo Hemorrhagic Fever

Crimean-Congo hemorrhagic fever (CCHF) is a highly severe and virulent viral disease of zoonotic origin, caused by a tick-born CCHF virus (CCHFV). The virus is endemic in many countries and has a mortality rate between 10% and 40%. As there is no licensed vaccine or therapeutic options available to treat CCHF, the present study was designed to focus on application of modern computational approaches to propose a multi-epitope vaccine (MEV) expressing antigenic determinants prioritized from the CCHFV genome. Integrated computational analyses revealed the presence of 9 immunodominant epitopes from Nucleoprotein (N), RNA dependent RNA polymerase (RdRp), Glycoprotein N (Gn/G2), and Glycoprotein C (Gc/G1). Together these epitopes were observed to cover 99.74% of the world populations. The epitopes demonstrated excellent binding affinity for the B- and T-cell reference set of alleles, the high antigenic potential, non-allergenic nature, excellent solubility, zero percent toxicity and interferon-gamma induction potential. The epitopes were engineered into an MEV through suitable linkers and adjuvating with an appropriate adjuvant molecule. The recombinant vaccine sequence revealed all favorable physicochemical properties allowing the ease of experimental analysis in vivo and in vitro. The vaccine 3D structure was established ab initio. Furthermore, the vaccine displayed excellent binding affinity for critical innate immune receptors: TLR2 (−14.33 kcal/mol) and TLR3 (−6.95 kcal/mol). Vaccine binding with these receptors was dynamically analyzed in terms of complex stability and interaction energetics. Finally, we speculate the vaccine sequence reported here has excellent potential to evoke protective and specific immune responses subject to evaluation of downstream experimental analysis.

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