Peripheral blood natural killer cells in Crimean-Congo hemorrhagic fever

Yılmaz, Mustafa; Aydın, Kemalettin; Akdoğan, Elif; Sucu, Nurgün; Sönmez, Mehmet; Omay, Serdar Bedii; Köksal, İftihar

doi:10.1016/j.jcv.2008.03.003

Cited by 28 publications

(19 citation statements)

References 12 publications

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“…In the second study, the NK cell counts were unchanged, while higher CTL counts correlated with both fatal cases and a higher viral load. However, this study looked at percentages and not absolute counts (38). In our study, the lymphocyte and APC populations in the spleen were activated within 3 dpi.…”

Section: Vol 84 2010 New Animal Model For Crimean-congo Hemorrhagicmentioning

confidence: 77%

“…However, evidence from human infections suggests immunological correlations with death. Two studies have looked at T, B, and NK cells in CCHF cases with contradicting results (1,38). The first study correlated an increase in total NK numbers with severe cases of CCHF, where the highest NK cell counts occurred in fatal cases.…”

Section: Vol 84 2010 New Animal Model For Crimean-congo Hemorrhagicmentioning

confidence: 99%

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Pathogenesis and Immune Response of Crimean-Congo Hemorrhagic Fever Virus in a STAT-1 Knockout Mouse Model

Bente

Alimonti

Shieh

et al. 2010

J Virol

216

242

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Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe hemorrhagic syndrome in humans but not in its vertebrate animal hosts. The pathogenesis of the disease is largely not understood due to the lack of an animal model. Laboratory animals typically show no overt signs of disease. Here, we describe a new small-animal model to study CCHFV pathogenesis that manifests clinical disease, similar to that seen in humans, without adaptation of the virus to the host. Our studies revealed that mice deficient in the STAT-1 signaling molecule were highly susceptible to infection, succumbing within 3 to 5 days. After CCHFV challenge, mice exhibited fever, leukopenia, thrombocytopenia, and highly elevated liver enzymes. Rapid viremic dissemination and extensive replication in visceral organs, mainly in liver and spleen, were associated with prominent histopathologic changes in these organs. Dramatically elevated proinflammatory cytokine levels were detected in the blood of the animals, suggestive of a cytokine storm. Immunologic analysis revealed delayed immune cell activation and intensive lymphocyte depletion. Furthermore, this study also demonstrated that ribavirin, a suggested treatment in human cases, protects mice from lethal CCHFV challenge. In conclusion, our data demonstrate that the interferon response is crucial in controlling CCHFV replication in this model, and this is the first study that offers an in-depth in vivo analysis of CCHFV pathophysiology. This new mouse model exhibits key features of fatal human CCHF, proves useful for the testing of therapeutic strategies, and can be used to study virus attenuation.

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Section: Vol 84 2010 New Animal Model For Crimean-congo Hemorrhagicmentioning

confidence: 77%

Section: Vol 84 2010 New Animal Model For Crimean-congo Hemorrhagicmentioning

confidence: 99%

Pathogenesis and Immune Response of Crimean-Congo Hemorrhagic Fever Virus in a STAT-1 Knockout Mouse Model

Bente

Alimonti

Shieh

et al. 2010

J Virol

216

242

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“…Nitric oxide (NO), a mediator of innate responses, also suppresses CCHFV replication (Simon et al, 2006). A recent study found that natural killer (NK) cells appear to play a role in the host response to CCHF, as greater numbers of circulating NK cells were observed in severe than mild cases, as indicated by serum liver enzyme levels; the highest counts were seen in two fatal cases (Yilmaz et al, 2008). Another study showed a higher percentage of cytotoxic T cells among circulating lymphocytes in fatal than nonfatal cases; the percentage correlated with viral load (Akinci et al, 2009).…”

Section: Pathogenesis Of Cchfmentioning

confidence: 99%

Crimean-Congo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity

et al. 2013

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Bente, Dennis A.; Forrester, Naomi L.; Watts, Douglas M.; McAuley, Alexander J.; Whitehouse, Chris A.; and Bray, Mike, "CrimeanCongo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity" (2013 b s t r a c tCrimean-Congo hemorrhagic fever (CCHF) is the most important tick-borne viral disease of humans, causing sporadic cases or outbreaks of severe illness across a huge geographic area, from western China to the Middle East and southeastern Europe and throughout most of Africa. CCHFV is maintained in vertical and horizontal transmission cycles involving ixodid ticks and a variety of wild and domestic vertebrates, which do not show signs of illness. The virus circulates in a number of tick genera, but Hyalomma ticks are the principal source of human infection, probably because both immature and adult forms actively seek hosts for the blood meals required at each stage of maturation. CCHF occurs most frequently among agricultural workers following the bite of an infected tick, and to a lesser extent among slaughterhouse workers exposed to the blood and tissues of infected livestock and medical personnel through contact with the body fluids of infected patients. CCHFV is the most genetically diverse of the arboviruses, with nucleotide sequence differences among isolates ranging from 20% for the viral S segment to 31% for the M segment. Viruses with diverse sequences can be found within the same geographic area, while closely related viruses have been isolated in far distant regions, suggesting that widespread dispersion of CCHFV has occurred at times in the past, possibly by ticks carried on migratory birds or through the international livestock trade. Reassortment among genome segments during co-infection of ticks or vertebrates appears to have played an important role in generating diversity, and represents a potential future source of novel viruses. In this article, we first review current knowledge of CCHFV, summarizing its molecular biology, maintenance and transmission, epidemiology and geographic range. We also include an extensive discussion of CCHFV genetic diversity, including maps of the range of the virus with superimposed phylogenetic trees. We then review the features of CCHF, including the clinical syndrome, diagnosis, treatment, pathogenesis, vaccine development and laboratory animal models of CCHF. The paper ends with a discussion of the possible future geographic range of the virus. For the benefit of researchers, we include a Supplementary Table listing all published reports of CCHF cases and outbreaks in the English-language literature, plus some principal articles in other languages, with total case numbers, case fatality rates and all CCHFV strains on GenBank.

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“…During CCHFV infection, apart from the activated macrophages, an increase in the numbers of natural killer cells and CD3+ CD8+ T cells is observed (Yilmaz et al, 2008; Akinci et al, 2009). But as the disease progresses, the uncontrolled apoptosis of lymphocytes contributes to a depletion in lymphocyte counts, which is presented as lymphopenia (Bente et al, 2010).…”

Section: Host-pathogen Interactionsmentioning

confidence: 99%

Crimean-Congo Hemorrhagic Fever: Tick-Host-Virus Interactions

Papa

Tsergouli

Tsioka

et al. 2017

Front. Cell. Infect. Microbiol.

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Crimean-Congo hemorrhagic fever virus (CCHFV) is transmitted to humans by bite of infected ticks or by direct contact with blood or tissues of viremic patients or animals. It causes to humans a severe disease with fatality up to 30%. The current knowledge about the vector-host-CCHFV interactions is very limited due to the high-level containment required for CCHFV studies. Among ticks, Hyalomma spp. are considered the most competent virus vectors. CCHFV evades the tick immune response, and following its replication in the lining of the tick's midgut, it is disseminated by the hemolymph in the salivary glands and reproductive organs. The introduction of salivary gland secretions into the host cells is the major route via which CCHFV enters the host. Following an initial amplification at the site of inoculation, the virus is spread to the target organs. Apoptosis is induced via both intrinsic and extrinsic pathways. Genetic factors and immune status of the host may affect the release of cytokines which play a major role in disease progression and outcome. It is expected that the use of new technology of metabolomics, transcriptomics and proteomics will lead to improved understanding of CCHFV-host interactions and identify potential targets for blocking the CCHFV transmission.

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Peripheral blood natural killer cells in Crimean-Congo hemorrhagic fever

Cited by 28 publications

References 12 publications

Pathogenesis and Immune Response of Crimean-Congo Hemorrhagic Fever Virus in a STAT-1 Knockout Mouse Model

Pathogenesis and Immune Response of Crimean-Congo Hemorrhagic Fever Virus in a STAT-1 Knockout Mouse Model

Crimean-Congo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity

Crimean-Congo Hemorrhagic Fever: Tick-Host-Virus Interactions

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