Interacting Roles of Immune Mechanisms and Viral Load in the Pathogenesis of Crimean-Congo Hemorrhagic Fever

Saksida, Ana; Duh, Darja; Wraber, Branka; Dedushaj, Isuf; Ahmeti, Salih; Avšič–Županc, Tatjana

doi:10.1128/cvi.00530-09

Cited by 126 publications

(165 citation statements)

References 42 publications

Supporting

Mentioning

147

Contrasting

Unclassified

Order By: Relevance

“…Similar observations have been made in Kosovo and Albania (Duh et al, 2007;Papa et al, 2006). Studies in both countries have shown that serum viral load is directly related to disease severity (Ergonul et al, 2006b;Saksida et al, 2010). In Kosovo, fatally infected patients had the highest levels of TNF-a, IFN-c and IL-10, while the Turkish study found that fatality was correlated with elevated IL-6 and TNF-a, but not IL-10.…”

Section: Predictors Of Survival or Deathsupporting

confidence: 62%

“…Early studies in South Africa found that most patients who went onto survive the disease had detectable anti-CCHFV IgM by day 7 and IgG by day 7-9 of illness, while no response was detected in fatally infected individuals (Burt et al, 1994;Shepherd et al, 1989c;van Eeden et al, 1985b). The correlation of antibody responses with survival has been demonstrated more recently in patients in Turkey and Kosovo (Ergonul et al, 2006a;Saksida et al, 2010).…”

Section: Predictors Of Survival or Deathmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2013

View full text Add to dashboard Cite

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.

show abstract

Section: Predictors Of Survival or Deathsupporting

confidence: 62%

Section: Predictors Of Survival or Deathmentioning

confidence: 99%

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

et al. 2013

View full text Add to dashboard Cite

show abstract

“…A direct correlation between the severity of disease for CCHF and a high viral load had already been observed in several patient studies (9,14,33), although the molecular mechanisms underlying this observation were not further elucidated. We tentatively speculate that the mechanism underlying the correlation between high viral load and disease severity in patients could be caused in part by the virus-enhanced endothelial cell activation, followed by excessive inflammatory reactions and leukocyte recruitment.…”

Section: Fig 2 Activation Of Endothelial Cells Is Virus Dose Dependmentioning

confidence: 99%

“…Elevated serum levels of the proinflammatory cytokines interleukin 6 (IL-6) and TNF-␣ were correlated with CCHF disease severity in several patient studies, and IL-8 levels were increased in a fatal case of CCHF in Greece (16,28,29,33). These cytokines were also released from CCHFV-infected dendritic cells (DCs) and macrophages (11,30).…”

mentioning

confidence: 92%

See 1 more Smart Citation

Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells

Connolly‐Andersen

Moll

Andersson

et al. 2011

J Virol

View full text Add to dashboard Cite

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.

show abstract

Lateral Flow Immunoassays – from Paper Strip to Smartphone Technology

et al. 2015

View full text Add to dashboard Cite

Cyclic peptides are important natural products and hold great promise for the identification of new bioactive molecules. The split‐intein‐mediated SICLOPPS technology provides a generic access to fully genetically encoded head‐to‐tail cyclized peptides and large libraries thereof (SICLOPPS=split‐intein circular ligation of peptides and proteins). However, owing to the spontaneous protein splicing reaction, product formation occurs inside cells, making peptide isolation inconvenient and precluding traditional in vitro assays for inhibitor discovery. The design of a genetically encoded, light‐dependent intein using the photocaged tyrosine derivative ortho‐nitrobenzyltyrosine incorporated at an internal, non‐catalytic position is now reported. Stable intein precursors were purified from the E. coli expression host and subsequently subjected to light activation in vitro for both the regular protein splicing format and cyclic peptide production, including the natural product segetalin H as an example. The activity of the intein could also be triggered in living cells.

show abstract

Interacting Roles of Immune Mechanisms and Viral Load in the Pathogenesis of Crimean-Congo Hemorrhagic Fever

Cited by 126 publications

References 42 publications

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

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

Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells

Lateral Flow Immunoassays – from Paper Strip to Smartphone Technology

Contact Info

Product

Resources

About