scholarly journals Reverse Genetics for Crimean-Congo Hemorrhagic Fever Virus

2003 ◽  
Vol 77 (10) ◽  
pp. 5997-6006 ◽  
Author(s):  
Ramon Flick ◽  
Kirsten Flick ◽  
Heinz Feldmann ◽  
Fredrik Elgh
Keyword(s):  
Reporter Gene ◽  
Reverse Genetics ◽  
Hemorrhagic Fever ◽  
Eukaryotic Cell ◽  
Health Concern ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Pol I ◽  
Prophylactic Measures ◽  
Cchf Virus

ABSTRACT The widespread geographical distribution of Crimean-Congo hemorrhagic fever (CCHF) virus (more than 30 countries) and its ability to produce severe human disease with high mortality rates (up to 60%) make CCHF a major public health concern worldwide. We describe here the successful establishment of a reverse genetics technology for CCHF virus, a member of the genus Nairovirus, family Bunyaviridae. The RNA polymerase I (pol I) system was used to generate artificial viral RNA genome segments (minigenomes), which contained different reporter genes in antisense (virus RNA) or sense (virus-complementary RNA) orientation flanked by the noncoding regions of the CCHF virus S segment. Reporter gene expression was observed in different eukaryotic cell lines following transfection and subsequent superinfection with CCHF virus, confirming encapsidation, transcription, and replication of the pol I-derived minigenomes. The successful transfer of reporter gene activity to fresh cells demonstrated the generation of recombinant CCHF viruses, thereby confirming the packaging of the pol I-derived minigenomes into progeny viruses. The system offers a unique opportunity to study the biology of nairoviruses and to develop therapeutic and prophylactic measures against CCHF infections. In addition, we demonstrated for the first time that the human pol I system can be used to develop reverse genetics approaches for viruses in the family Bunyaviridae. This is important since it might facilitate the manipulation of bunyaviruses with cell and host tropisms restricted to primates.

scholarly journals Differential Cell Line Susceptibility to Crimean-Congo Hemorrhagic Fever Virus

2021 ◽  
Vol 11 ◽  
Author(s):  
Shiyu Dai ◽  
Qiaoli Wu ◽  
Xiaoli Wu ◽  
Cheng Peng ◽  
Jia Liu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Ex Vivo ◽  
Animal Cell ◽  
Hemorrhagic Fever ◽  
Viral Disease ◽  
Permissive Cell ◽  
Hek 293 ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Cchf Virus

Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne viral disease of global concerns due to the increasing incidence and lack of effective treatments. The causative agent, CCHF virus (CCHFV), has been characterized for years; however, its tropism in cell lines of different host and tissue origins remains unclear. This study characterized the susceptibility of 16 human and 6 animal cell lines to CCHFV. Increased viral load and viral nucleoprotein expression, and productive CCHFV replication were detected in human vascular (HUVEC), renal (SW-13 and HEK-293), hepatic (Huh7), and cerebral (U-87 MG) cell lines, which were considered CCHFV-highly permissive cell lines. Renal cell lines derived from monkey and dog could also support CCHFV replication. This study evaluated the susceptibility of different cell lines to CCHFV and identified CCHFV-permissive cell lines. Our findings raise concerns regarding the use of cell lines in ex vivo studies of CCHFV and may have important implications for further fundamental research, which would promote understanding of CCHFV pathogenesis and transmission, as well as benefit designing strategies for disease prevention and control.

scholarly journals Recent advances in understanding Crimean–Congo hemorrhagic fever virus

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1715 ◽  
Author(s):  
David W. Hawman ◽  
Heinz Feldmann
Keyword(s):  
Reverse Genetics ◽  
Small Animal ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Hemorrhagic Disease ◽  
Crimean Congo Hemorrhagic Fever ◽  
Host Restriction ◽  
Hemorrhagic Fever Virus ◽  
Recent Emergence ◽  
Viral Determinants

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed hemorrhagic fever virus and the cause of hemorrhagic disease in Africa, Southern and Eastern Europe, the Middle East, India and Asia. Recent emergence of CCHFV into Spain indicates that the geographic range of this virus is expanding and the presence of its tick vector in several countries without reported disease suggest that CCHFV will continue to spread. Research into CCHFV was historically limited by a lack of suitable animal models and tools to study viral pathogenesis. However, in the past few years the toolset for studying CCHFV has expanded with small animal and non-human primate models for CCHFV being developed along with a reverse genetics system that allows for investigation of viral determinants of disease. These tools have been utilized to understand how CCHFV antagonizes host restriction factors and to develop novel vaccine candidates that may help limit the substantial morbidity and mortality in humans caused by CCHFV.

scholarly journals Evidence for recombination in Crimean-Congo hemorrhagic fever virus

2005 ◽  
Vol 86 (8) ◽  
pp. 2333-2338 ◽  
Author(s):  
Alexander N. Lukashev
Keyword(s):  
Phylogenetic Trees ◽  
Hemorrhagic Fever ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Bootscan Analysis ◽  
Phylogenetic Studies ◽  
Cchf Virus ◽  
L Segment ◽  
Virus Strains ◽  
Multiple Recombination

Crimean-Congo hemorrhagic fever (CCHF) virus has attracted considerable attention recently and a number of phylogenetic studies have been published, based mostly on partial sequences of S and M RNA segments. In this study, available full-length S, M and L segment sequences of CCHF virus were checked for recombination. Similarity plots and bootscan analysis of the S segment suggested multiple recombination events between southern European, Asian and African CCHF virus strains, with additional evidence provided by phylogenetic trees, the hidden Markov model and probabilistic divergence measures methods. No unambiguous signs of recombination were observed for M and L segments; however, the results did not exclude the possibility of this. These findings, coupled with a recent report on reassortment in CCHF virus, suggest caution when assessing CCHF virus phylogeny based on short sequence fragments.

scholarly journals Crimean-Congo Hemorrhagic Fever Virus Genomics and Global Diversity

2006 ◽  
Vol 80 (17) ◽  
pp. 8834-8842 ◽  
Author(s):  
Varough M. Deyde ◽  
Marina L. Khristova ◽  
Pierre E. Rollin ◽  
Thomas G. Ksiazek ◽  
Stuart T. Nichol
Keyword(s):  
Genetic Recombination ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Severe Illness ◽  
Long Distance ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Individual Segment ◽  
Cchf Virus ◽  
Tree Topologies

ABSTRACT Crimean-Congo hemorrhagic fever (CCHF) is a severe illness with high case fatality that occurs in Africa, Europe, the Middle East, and Asia. The complete genomes of 13 geographically and temporally diverse virus strains were determined, and CCHF viruses were found to be highly variable with 20 and 8%, 31 and 27%, and 22 and 10% nucleotide and deduced amino acid differences detected among virus S (nucleocapsid), M (glycoprotein), and L (polymerase) genome segments, respectively. Distinct geographic lineages exist, but with multiple exceptions indicative of long-distance virus movement. Discrepancies among the virus S, M, and L phylogenetic tree topologies document multiple RNA segment reassortment events. An analysis of individual segment datasets suggests genetic recombination also occurs. For an arthropod-borne virus, the genomic plasticity of CCHF virus is surprisingly high.

scholarly journals Development of double antibody sandwich ELISA as potential diagnostic tool for rapid detection of Crimean-Congo hemorrhagic fever virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Neha Shrivastava ◽  
Jyoti S. Kumar ◽  
Pragya Yadav ◽  
Anita M. Shete ◽  
Rajlaxmi Jain ◽  
...  
Keyword(s):  
Detection Limit ◽  
Sensitivity And Specificity ◽  
Culture Supernatant ◽  
Sandwich Elisa ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Double Antibody ◽  
Cchf Virus

AbstractCrimean-Congo hemorrhagic fever (CCHF) virus, a highly pathogenic viral agent is responsible for severe fatal hemorrhagic infections in many parts of the world. The early diagnosis of CCHF infection is important for successful clinical management and epidemiological control. The nucleoprotein (NP) of CCHFV being highly conserved and immunogenic is used as early diagnostic marker. In this study, we report a rapid and sensitive double antibody based antigen capture ELISA to detect Crimean-Congo hemorrhagic fever virus (CCHFV). Highly specific polyclonal and monoclonal antibody against NP has been generated and used as capture and detector antibody respectively. The assay was able to detect viral nucleoprotein in different matrices including human serum, ticks and culture supernatant. The detection limit of the developed sandwich ELISA assay was 25 ng of purified antigen. Comparison with a real time RT-PCR revealed its detection limit to be 1000 genome equivalents of CCHFV. Further the assay was comparatively evaluated with a commercial kit employing gamma irradiated CCHFV, revealing a sensitivity and specificity of 100%. This newly developed sandwich ELISA (sELISA) with high sensitivity and specificity could be used as an efficient method for the detection of CCHF virus in humans, ticks and culture supernatant. The assay will be useful as alternate tool for diagnosis of acute infection and is amenable for screening of large scale samples in resource limited settings.

scholarly journals Serologic and molecular evidence for circulation of Crimean-Congo hemorrhagic fever virus in ticks and cattle in Zambia

2021 ◽  
Vol 15 (6) ◽  
pp. e0009452
Author(s):  
Masahiro Kajihara ◽  
Martin Simuunza ◽  
Ngonda Saasa ◽  
George Dautu ◽  
Akina Mori-Kajihara ◽  
...  
Keyword(s):  
Phylogenetic Analyses ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Epidemiologic Studies ◽  
Immunofluorescence Assay ◽  
Molecular Evidence ◽  
African Countries ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Cchf Virus

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonosis with a high case fatality rate in humans. Although the disease is widely found in Africa, Europe, and Asia, the distribution and genetic diversity of CCHF virus (CCHFV) are poorly understood in African countries. To assess the risks of CCHF in Zambia, where CCHF has never been reported, epidemiologic studies in cattle and ticks were conducted. Through an indirect immunofluorescence assay, CCHFV nucleoprotein-specific serum IgG was detected in 8.4% (88/1,047) of cattle. Among 290 Hyalomma ticks, the principal vector of CCHFV, the viral genome was detected in 11 ticks. Phylogenetic analyses of the CCHFV S and M genome segments revealed that one of the detected viruses was a genetic reassortant between African and Asian strains. This study provides compelling evidence for the presence of CCHFV in Zambia and its transmission to vertebrate hosts.

scholarly journals The world areal of Crimean-Congo hemorrhagic fever virus

2006 ◽  
Vol 5 ◽  
pp. 79-86 ◽  
Author(s):  
S. Ye. Smirnova
Keyword(s):  
Hemorrhagic Fever ◽  
Domestic Animals ◽  
Fever Virus ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Immunological Status ◽  
The World ◽  
Cchf Virus

Distribution of Crimean-Congo hemorrhagic fever (CCHF) virus based on virus isolations and results of seroepidemiological surveys. The were investigated 147 cases of ill (4 countries of Europe and Asia), immunological status of population (13 countries of Europe, Asia and Africa) and domestic animals (16 countries of Europe, Asia and Africa) and infected ticks (7 countries of Eu- rope and Asia). CCHF was first recognized in Azerbaijan, Armenia, Afghanistan, Iran, India and confirmed in Russia, Ukraine, Bulgaria, Yugoslavia (Europe), Uzbekistan, Tadzhikistan, Turkmenistan, Kazakhstan (Asia) and Uganda, Senegal, Kenya (Africa).

scholarly journals A single mutation in Crimean-Congo hemorrhagic fever virus discovered in ticks impairs infectivity in human cells

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Brian L Hua ◽  
Florine EM Scholte ◽  
Valerie Ohlendorf ◽  
Anne Kopp ◽  
Marco Marklewitz ◽  
...  
Keyword(s):  
Genomic Sequence ◽  
Hemorrhagic Fever ◽  
Human Cells ◽  
Genomic Diversity ◽  
Single Mutation ◽  
Viral Glycoprotein ◽  
Glycoprotein Precursor ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Cchf Virus

Crimean-Congo hemorrhagic fever (CCHF) is the most widely distributed tick-borne viral infection in the world. Strikingly, reported mortality rates for CCHF are extremely variable, ranging from 5% to 80% (Whitehouse, 2004). CCHF virus (CCHFV, Nairoviridae) exhibits extensive genomic sequence diversity across strains (Deyde et al., 2006; Sherifi et al., 2014). It is currently unknown if genomic diversity is a factor contributing to variation in its pathogenicity. We obtained complete genome sequences of CCHFV directly from the tick reservoir. These new strains belong to a solitary lineage named Europe 2 that is circumstantially reputed to be less pathogenic than the epidemic strains from Europe 1 lineage. We identified a single tick-specific amino acid variant in the viral glycoprotein region that dramatically reduces its fusion activity in human cells, providing evidence that a glycoprotein precursor variant, present in ticks, has severely impaired function in human cells.

scholarly journals Spatial Distribution of Ticks (Arachniada: Argasidae and Ixodidae) and Their Infection Rate to Crimean-Congo Hemorrhagic Fever Virus in Iran

2021 ◽  
Author(s):  
Ahmad Ali Hanafi-Bojd ◽  
Samin Jafari ◽  
Zakkyeh Telmadarraiy ◽  
Abbas Abbasi-Ghahramanloo ◽  
Eslam Moradi-Asl
Keyword(s):  
Invasive Species ◽  
Spatial Distribution ◽  
Hemorrhagic Fever ◽  
High Rate ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hard Ticks ◽  
Hemorrhagic Fever Virus ◽  
The Past ◽  
Hyalomma Marginatum ◽  
Cchf Virus

Background: The Crimean-Congo Hemorrhagic Fever (CCHF) is one of the most important arthropod-borne viral dis-eases with a mortality rate of about 30% among humans. The disease, caused by a Nairovirus, is transmitted to humans and animals by hard and soft ticks. This study aimed to determine the distribution of soft and hard ticks in the past three decades in Iran with an emphasis on the vectors of the CCHF virus. Methods: In this study, all studies that were carried out in different regions of Iran from 1979 to 2018 and their results were published in prestigious journals were used to create a database. The distribution of ticks was mapped using ArcMap10.3. Results: Based on the results, nine genera and 37 species of soft and hard ticks were recorded in Iran. So far, six genera and 16 species of hard and soft ticks were reported to be infected with the CCHF virus. The infection to this virus was reported from 18 out of 31 provinces, with a high rate in Sistan and Baluchistan as well as Khuzestan provinces. The highest levels of CCHF infection belonged to Hyalomma marginatum and H. anatolicum. Conclusion: The main vectors of CCHF, H. marginatum and H. anatolicum, were reported in more than 38.7% of Iran's provinces, and these two species were identified as invasive species in Iran. Thus, control activities should be strength-ened to avoid the outbreaks of CCHF.

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