Evidence of vascular endothelial damage in Crimean-Congo hemorrhagic fever

Bodur, Hürrem; Akıncı, Esragül; Öngürü, Pınar; Uyar, Yavuz; Baştürk, Bilkay; Gözel, Mustafa Gökhan; Kayaaslan, Bircan

doi:10.1016/j.ijid.2010.02.2240

Cited by 52 publications

(44 citation statements)

References 30 publications

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“…However, the direct interaction of CCHFV and ECs has been largely neglected, even though there are several indicators that ECs are involved in CCHF pathogenesis (4,6,27). To our knowledge, this is the first study focusing on the in vitro interaction between CCHFV and ECs.…”

Section: Discussionmentioning

confidence: 99%

“…In autopsies of deceased CCHF patients, viral antigen was present in endothelial cells (ECs) (6), and molecular endothelial activation markers correlated with disease severity (4,27). The involvement of the endothelium for CCHF and other VHFs has classically been explained by one of two theories: virus infection activates endothelial cells (i) directly or (ii) indirectly via infected leukocytes releasing soluble mediators with concomitant activation of the endothelium (20,34).…”

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confidence: 99%

“…ICAM1 is minimally expressed on resting endothelial cells and is upregulated in response to inflammatory mediators, such as virus infection and the proinflammatory cytokines IL-1␤, IL-6, and TNF-␣ (31,38). The activation marker soluble ICAM1 (sICAM1) (42) correlated with CCHF disease severity in two patient studies (4,27), although it is not yet known whether this marker is derived from endothelial cells or from leukocytes.…”

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confidence: 99%

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Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells

Connolly‐Andersen

Moll

Andersson

et al. 2011

J Virol

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Crimean-Congo hemorrhagic fever virus (CCHFV) causes viral hemorrhagic fever with high case-fatality rates and is geographically widely distributed. Due to the requirement for a biosafety level 4 (BSL-4) laboratory and the lack of an animal model, knowledge of the viral pathogenesis is limited. Crimean-Congo hemorrhagic fever (CCHF) is characterized by hemorrhage and vascular permeability, indicating the involvement of endothelial cells (ECs). The interplay between ECs and CCHFV is therefore important for understanding the pathogenesis of CCHF. In a previous study, we found that CCHFV-infected monocyte-derived dendritic cells (moDCs) activated ECs; however, the direct effect of CCHFV on ECs was not investigated. Here, we report that ECs are activated upon infection, as demonstrated by upregulation of mRNA levels for E-selectin, vascular cell adhesion molecule 1 (VCAM1), and intercellular adhesion molecule 1 (ICAM1). Protein levels and cell surface expression of ICAM1 responded in a dose-dependent manner to increasing CCHFV titers with concomitant increase in leukocyte adhesion. Furthermore, we examined vascular endothelial (VE) cadherin in CCHFVinfected ECs by different approaches. Infected ECs released higher levels of interleukin 6 (IL-6) and IL-8; however, stimulation of resting ECs with supernatants derived from infected ECs did not result in increased ICAM1 expression. Interestingly, the moDC-mediated activation of ECs was abrogated by addition of neutralizing tumor necrosis factor alpha (TNF-␣) antibody to moDC supernatants, thereby identifying this soluble mediator as the key cytokine causing EC activation. We conclude that CCHFV can exert both direct and indirect effects on ECs.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells

Connolly‐Andersen

Moll

Andersson

et al. 2011

J Virol

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“…Laboratory animal studies of Ebola HF, which shares many features with CCHF, suggest that altered vascular function results from host-induced mechanisms, including the induction of proinflammatory cytokines, platelet aggregation and degranulation, leukocyte adhesion and activation of the intrinsic coagulation cascade (Mahanty and Bray, 2004;Schnittler and Feldmann, 2003). Two recent studies in Turkey found that serum markers of vascular activation, including sICAM-1 and sVCAM-1, were elevated in CCHF patients, and were higher in fatal cases (Ozturk et al, 2010;Bodur et al, 2010); conflicting results were obtained for the marker VEGF. CCHFV infection of cultured human endothelial cells has been shown to cause up-regulation of ICAM-1 and VCAM-1 and the secretion of IL-6 and IL-8 (Connolly-Andersen 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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“…Despite these data, it remains unclear how tick-induced changes at the tick-dermal interface permeability, resulting in hypotension, shock, multiple organ failure and death (22)(23)(24)(25). The proinflammatory cytokines may be the reason for the CCHF dermatological signs (morbilliform eruptions, petechial lesions, purpura, ecchymosis and oral erythema-petechiae), and they are secreted after endothelial injury.…”

Section: Nonspecific Skin Rashes Have Been Reported In Babesiosis Andmentioning

confidence: 99%

Cutaneous Findings of Crimean-Congo Hemorrhagic Fever: a Study of 269 Cases

et al. 2018

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A c c e p t e d M a n u s c r i p t 2 SummaryCrimean-Congo haemorrhagic fever (CCHF) is a viral zoonotic disease. We aimed here in this study to investigate the cutaneous manifestations of CCHF and reveal their associations with fatality. Two hundred and sixty-nine patients diagnosed with CCHF were recorded. Skin findings were seen in 170 (63.1%) patients. A facial rash was most common cutaneous finding (82 (30.4%)). In the severe cases, haemorrhagic cutaneous manifestations (petechiae and ecchymoses) were recognised. A statistically significant correlation was obtained between the cutaneous manifestations and fatality, and it was determined that there was a strong positive correlation between the fatality and ecchymosis (r=567, p<0.001). In addition, a logistic regression analysis was performed, and death occurred 4.69 times more in those with skin signs than in those without. We hypothesize that CCHF patients with ecchymosis are at the highest risk, and that the cutaneous findings can contribute the prognosis of CCHF.A c c e p t e d M a n u s c r i p t 3

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Evidence of vascular endothelial damage in Crimean-Congo hemorrhagic fever

Abstract: Endothelial activation can affect the course of CCHF, and vascular endothelial damage is probably indirect. Further studies are needed for general conclusions to be drawn.

Cited by 52 publications

References 30 publications

Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells

Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells

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

Cutaneous Findings of Crimean-Congo Hemorrhagic Fever: a Study of 269 Cases

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