scholarly journals Crimean–Congo Hemorrhagic Fever Virus Past Infections Are Associated with Two Innate Immune Response Candidate Genes in Dromedaries

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 8
Author(s):  
Sara Lado ◽  
Jan Futas ◽  
Martin Plasil ◽  
Tom Loney ◽  
Pia Weidinger ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Linear Regression Analysis ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Immune Defense ◽  
Innate Immune ◽  
Fever Virus ◽  
Future Research ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus

Dromedaries are an important livestock, used as beasts of burden and for meat and milk production. However, they can act as an intermediate source or vector for transmitting zoonotic viruses to humans, such as the Middle East respiratory syndrome coronavirus (MERS-CoV) or Crimean–Congo hemorrhagic fever virus (CCHFV). After several outbreaks of CCHFV in the Arabian Peninsula, recent studies have demonstrated that CCHFV is endemic in dromedaries and camel ticks in the United Arab Emirates (UAE). There is no apparent disease in dromedaries after the bite of infected ticks; in contrast, fever, myalgia, lymphadenopathy, and petechial hemorrhaging are common symptoms in humans, with a case fatality ratio of up to 40%. We used the in-solution hybridization capture of 100 annotated immune genes to genotype 121 dromedaries from the UAE tested for seropositivity to CCHFV. Through univariate linear regression analysis, we identified two candidate genes belonging to the innate immune system: FCAR and CLEC2B. These genes have important functions in the host defense against viral infections and in stimulating natural killer cells, respectively. This study opens doors for future research into immune defense mechanisms in an enzootic host against an important zoonotic disease.

Crimean-Congo hemorrhagic fever virus delays activation of the innate immune response

2008 ◽  
Vol 80 (8) ◽  
pp. 1397-1404 ◽  
Author(s):  
Ida Andersson ◽  
Helen Karlberg ◽  
Mehrdad Mousavi-Jazi ◽  
Luis Martínez-Sobrido ◽  
Friedemann Weber ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Hemorrhagic Fever ◽  
Innate Immune ◽  
Fever Virus ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus

scholarly journals Worldwide epidemiology of Crimean-Congo Hemorrhagic Fever Virus in humans, ticks and other animal species, a systematic review and meta-analysis

2021 ◽  
Vol 15 (4) ◽  
pp. e0009299
Author(s):  
Jean Thierry Ebogo Belobo ◽  
Sebastien Kenmoe ◽  
Cyprien Kengne-Nde ◽  
Cynthia Paola Demeni Emoh ◽  
Arnol Bowo-Ngandji ◽  
...  
Keyword(s):  
Systematic Review ◽  
Low Income ◽  
Animal Species ◽  
Meta Analysis ◽  
Random Effect ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus

There are uncertainties about the global epidemiological data of infections due to Crimean-Congo hemorrhagic fever virus (CCHFV). We estimated the global case fatality rate (CFR) of CCHFV infections and the prevalence of CCHFV in humans, ticks and other animal species. We also explored the socio-demographic and clinical factors that influence these parameters. In this systematic review with meta–analyses we searched publications from database inception to 03rd February 2020 in Pubmed, Scopus, and Global Index Medicus. Studies included in this review provided cross-sectional data on the CFR and/or prevalence of one or more targets used for the detection of CCHFV. Two independent investigators selected studies to be included. Data extraction and risk of bias assessment were conducted independently by all authors. Data collected were analysed using a random effect meta-analysis. In all, 2345 records were found and a total of 312 articles (802 prevalence and/or CFR data) that met the inclusion criteria were retained. The overall CFR was 11.7% (95% CI = 9.1–14.5), 8.0% (95% CI = 1.0–18.9), and 4.7% (95% CI = 0.0–37.6) in humans with acute, recent, and past CCHFV infections respectively. The overall CCHFV acute infections prevalence was 22.5% (95% CI = 15.7–30.1) in humans, 2.1% (95% CI = 1.3–2.9) in ticks, and 4.5% (95% CI = 1.9–7.9) in other animal species. The overall CCHFV recent infections seroprevalence was 11.6% (95% CI = 7.9–16.4) in humans and 0.4% (95% CI = 0.0–2.9) in other animal species. The overall CCHFV past infections seroprevalence was 4.3% (95% CI = 3.3–5.4) in humans and 12.0% (95% CI = 9.9–14.3) in other animal species. CFR was higher in low-income countries, countries in the WHO African, South-East Asia and Eastern Mediterranean regions, in adult and ambulatory patients. CCHFV detection rate in humans were higher in CCHFV suspected cases, healthcare workers, adult and hospitalized patients, ticks of the genus Ornithodoros and Amblyomma and in animals of the orders Perissodactyla and Bucerotiformes. This review highlights a significant disease burden due to CCHFV with a strong disparity according to country income levels, geographic regions, various human categories and tick and other animal species. Preventive measures in the light of these findings are expected.

scholarly journals Crimean-Congo Hemorrhagic Fever Virus Suppresses Innate Immune Responses via a Ubiquitin and ISG15 Specific Protease

Cell Reports ◽  
2017 ◽  
Vol 20 (10) ◽  
pp. 2396-2407 ◽  
Author(s):  
Florine E.M. Scholte ◽  
Marko Zivcec ◽  
John V. Dzimianski ◽  
Michelle K. Deaton ◽  
Jessica R. Spengler ◽  
...  
Keyword(s):  
Immune Responses ◽  
Hemorrhagic Fever ◽  
Innate Immune ◽  
Fever Virus ◽  
Innate Immune Responses ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Specific Protease

scholarly journals Immunocompetent mouse model for Crimean-Congo hemorrhagic fever virus

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
David W Hawman ◽  
Kimberly Meade-White ◽  
Shanna Leventhal ◽  
Friederike Feldmann ◽  
Atsushi Okumura ◽  
...  
Keyword(s):  
Mouse Model ◽  
Severe Disease ◽  
Case Fatality ◽  
Febrile Illness ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Type I ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Viral Determinants

Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne febrile illness with wide geographic distribution. CCHF is caused by infection with the Crimean-Congo hemorrhagic fever virus (CCHFV) and case fatality rates can be as high as 30%. Despite causing severe disease in humans, our understanding of the host and viral determinants of CCHFV pathogenesis are limited. A major limitation in the investigation of CCHF has been the lack of suitable small animal models. Wild-type mice are resistant to clinical isolates of CCHFV and consequently, mice must be deficient in type I interferon responses to study the more severe aspects of CCHFV. We report here a mouse-adapted variant of CCHFV that recapitulates in adult, immunocompetent mice the severe CCHF observed in humans. This mouse-adapted variant of CCHFV significantly improves our ability to study host and viral determinants of CCHFV-induced disease in a highly tractable mouse model.

scholarly journals Immunocompetent Mouse Model for Crimean-Congo Hemorrhagic Fever Virus

2020 ◽  
Author(s):  
David W. Hawman ◽  
Kimberly Meade-White ◽  
Shanna Leventhal ◽  
Friederike Feldmann ◽  
Atsushi Okumura ◽  
...  
Keyword(s):  
Mouse Model ◽  
Severe Disease ◽  
Case Fatality ◽  
Febrile Illness ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Type I ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Viral Determinants

AbstractCrimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne febrile illness with wide geographic distribution. CCHF is caused by infection with the Crimean-Congo hemorrhagic fever virus (CCHFV) and case fatality rates can be as high as 30%. Despite causing severe disease in humans, our understanding of the host and viral determinants of CCHFV pathogenesis are limited. A major limitation in the investigation of CCHF has been the lack of suitable small animal models. Wild-type mice are resistant to clinical isolates of CCHFV and consequently, mice must be deficient in type I interferon responses to study the more severe aspects of CCHFV. We report here a mouse-adapted variant of CCHFV that recapitulates in adult, immunocompetent mice the severe CCHF observed in humans. This mouse-adapted variant of CCHFV significantly improves our ability to study host and viral determinants of CCHFV-induced disease in a highly tractable mouse model.

scholarly journals Immunogenicity of a DNA-Based Sindbis Replicon Expressing Crimean–Congo Hemorrhagic Fever Virus Nucleoprotein

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1491
Author(s):  
Thomas Tipih ◽  
Mark Heise ◽  
Felicity Jane Burt
Keyword(s):  
Immune Response ◽  
Sindbis Virus ◽  
Cytokine Production ◽  
Antiviral Drug ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Virus Vector ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus

Crimean–Congo hemorrhagic fever virus (CCHFV) infrequently causes hemorrhagic fever in humans with a case fatality rate of 30%. Currently, there is neither an internationally approved antiviral drug nor a vaccine against the virus. A replicon based on the Sindbis virus vector encoding the complete open reading frame of a CCHFV nucleoprotein from a South African isolate was prepared and investigated as a possible candidate vaccine. The transcription of CCHFV RNA and recombinant protein production by the replicon were characterized in transfected baby hamster kidney cells. A replicon encoding CCHFV nucleoprotein inserted in plasmid DNA, pSinCCHF-52S, directed transcription of CCHFV RNA in the transfected cells. NIH-III heterozygous mice immunized with pSinCCHF-52S generated CCHFV IgG specific antibodies with notably higher levels of IgG2a compared to IgG1. Splenocytes from mice immunized with pSinCCHF-52S secreted IFN-γ and IL-2, low levels of IL-6 or IL-10, and no IL-4. No specific cytokine production was registered in splenocytes of mock-immunized mice (p < 0.05). Thus, our study demonstrated the expression of CCHFV nucleoprotein by a Sindbis virus vector and its immunogenicity in mice. The spectrum of cytokine production and antibody profile indicated predominantly Th1-type of an anti-CCHFV immune response. Further studies in CCHFV-susceptible animals are necessary to determine whether the induced immune response is protective.

scholarly journals T-Cells and Interferon Gamma Are Necessary for Survival Following Crimean-Congo Hemorrhagic Fever Virus Infection in Mice

2021 ◽  
Vol 9 (2) ◽  
pp. 279
Author(s):  
David W. Hawman ◽  
Kimberly Meade-White ◽  
Shanna Leventhal ◽  
Aaron Carmody ◽  
Elaine Haddock ◽  
...  
Keyword(s):  
T Cells ◽  
Interferon Gamma ◽  
Severe Disease ◽  
Adaptive Immune Response ◽  
Case Fatality ◽  
Febrile Illness ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus

Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne febrile illness with wide geographic distribution. In humans, the disease follows infection by the Crimean-Congo hemorrhagic fever virus (CCHFV) and begins as flu-like symptoms that can rapidly progress to hemorrhaging and death. Case fatality rates can be as high as 30%. An important gap in our understanding of CCHF are the host immune responses necessary to control the infection. A better understanding of these responses is needed to direct therapeutic strategies to limit the often-severe morbidity and mortality seen in humans. In this report, we have utilized a mouse model in which mice develop severe disease but ultimately recover. T-cells were robustly activated, differentiated to produce antiviral cytokines, and were critical for survival following CCHFV infection. We further identified a key role for interferon gamma (IFNγ) in survival following CCHFV infection. These results significantly improve our understanding of the host adaptive immune response to severe CCHFV infection.

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