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Lübeck, Germany

Hombach A.,Bernhard Nocht Institute for Tropical Medicine | Ommen G.,Bernhard Nocht Institute for Tropical Medicine | Ommen G.,Euroimmun AG | MacDonald A.,Bernhard Nocht Institute for Tropical Medicine | Clos J.,Bernhard Nocht Institute for Tropical Medicine
Journal of Cell Science | Year: 2014

Leishmania parasites must survive and proliferate in two vastly different environments - the guts of poikilothermic sandflies and the antigen-presenting cells of homeothermic mammals. The change of temperature during the transmission from sandflies to mammals is both a key trigger for the progression of their life cycle and for elevated synthesis of heat shock proteins, which have been implicated in their survival at higher temperatures. Although the functions of the main heat shock protein families in the Leishmania life cycle have been studied, nothing is known about the roles played by small heat shock proteins. Here, we present the first evidence for the pivotal role played by the Leishmania donovani 23-kDa heat shock protein (which we called HSP23), which is expressed preferentially during the mammalian stage where it assumes a perinuclear localisation. Loss of HSP23 causes increased sensitivity to chemical stressors and renders L. donovani non-viable at 37°C. Consequently, HSP23-null mutants are non-infectious to primary macrophages in vitro. All phenotypic effects could be abrogated by the introduction of a functional HSP23 transgene into the null mutant, confirming the specificity of the mutant phenotype. Thus, HSP23 expression is a prerequisite for L. donovani survival at mammalian host temperatures and a crucial virulence factor. © 2014. Published by The Company of Biologists Ltd. Source


Muller M.A.,University of Bonn | Corman V.M.,University of Bonn | Corman V.M.,German Center for Infection Research | Jores J.,Kenya International Livestock Research Institute | And 9 more authors.
Emerging Infectious Diseases | Year: 2014

To analyze the distribution of Middle East respiratory syndrome coronavirus (MERS-CoV)–seropositive dromedary camels in eastern Africa, we tested 189 archived serum samples accumulated during the past 30 years. We identified MERS-CoV neutralizing antibodies in 81.0% of samples from the main camel-exporting countries, Sudan and Somalia, suggesting long-term virus circulation in these animals. © 2014, Centers for Disease Control and Prevention (CDC). All rights reserved. Source


Burkhardt C.,London School of Hygiene and Tropical Medicine | Burkhardt C.,Euroimmun AG | Sung P.-Y.,London School of Hygiene and Tropical Medicine | Celma C.C.,London School of Hygiene and Tropical Medicine | Roy P.,London School of Hygiene and Tropical Medicine
Journal of General Virology | Year: 2014

The mechanism used by bluetongue virus (BTV) to ensure the sorting and packaging of its 10 genomic segments is still poorly understood. In this study, we investigated the packaging constraints for two BTV genomic segments from two different serotypes. Segment 4 (S4) of BTV serotype 9 was mutated sequentially and packaging of mutant ssRNAs was investigated by two newly developed RNA packaging assay systems, one in vivo and the other in vitro. Modelling of the mutated ssRNA followed by biochemical data analysis suggested that a conformational motif formed by interaction of the 5′ and 3′ ends of the molecule was necessary and sufficient for packaging. A similar structural signal was also identified in S8 of BTV serotype 1. Furthermore, the same conformational analysis of secondary structures for positive-sense ssRNAs was used to generate a chimeric segment that maintained the putative packaging motif but contained unrelated internal sequences. This chimeric segment was packaged successfully, confirming that the motif identified directs the correct packaging of the segment. © 2014 The Authors. Source


Muller M.A.,University of Bonn | Meyer B.,University of Bonn | Corman V.M.,University of Bonn | Corman V.M.,German Center for Infection Research | And 19 more authors.
The Lancet Infectious Diseases | Year: 2015

Background: Scientific evidence suggests that dromedary camels are the intermediary host for the Middle East respiratory syndrome coronavirus (MERS-CoV). However, the actual number of infections in people who have had contact with camels is unknown and most index patients cannot recall any such contact. We aimed to do a nationwide serosurvey in Saudi Arabia to establish the prevalence of MERS-CoV antibodies, both in the general population and in populations of individuals who have maximum exposure to camels. Methods: In the cross-sectional serosurvey, we tested human serum samples obtained from healthy individuals older than 15 years who attended primary health-care centres or participated in a national burden-of-disease study in all 13 provinces of Saudi Arabia. Additionally, we tested serum samples from shepherds and abattoir workers with occupational exposure to camels. Samples were screened by recombinant ELISA and MERS-CoV seropositivity was confirmed by recombinant immunofluorescence and plaque reduction neutralisation tests. We used two-tailed Mann Whitney U exact tests, χ2, and Fisher's exact tests to analyse the data. Findings: Between Dec 1, 2012, and Dec 1, 2013, we obtained individual serum samples from 10 009 individuals. Anti-MERS-CoV antibodies were confirmed in 15 (0·15%; 95% CI 0·09-0·24) of 10 009 people in six of the 13 provinces. The mean age of seropositive individuals was significantly younger than that of patients with reported, laboratory-confirmed, primary Middle Eastern respiratory syndrome (43·5 years [SD 17·3] vs 53·8 years [17·5]; p=0·008). Men had a higher antibody prevalence than did women (11 [0·25%] of 4341 vs two [0·05%] of 4378; p=0·028) and antibody prevalence was significantly higher in central versus coastal provinces (14 [0·26%] of 5479 vs one [0·02%] of 4529; p=0·003). Compared with the general population, seroprevalence of MERS-CoV antibodies was significantly increased by 15 times in shepherds (two [2·3%] of 87, p=0·0004) and by 23 times in slaughterhouse workers (five [3·6%] of 140; p<0·0001). Interpretation: Seroprevalence of MERS-CoV antibodies was significantly higher in camel-exposed individuals than in the general population. By simple multiplication, a projected 44 951 (95% CI 26 971-71 922) individuals older than 15 years might be seropositive for MERS-CoV in Saudi Arabia. These individuals might be the source of infection for patients with confirmed MERS who had no previous exposure to camels. Funding: European Union, German Centre for Infection Research, Federal Ministry of Education and Research, German Research Council, and Ministry of Health of Saudi Arabia. © 2015 Elsevier Ltd. Source


Corman V.M.,University of Bonn | Jores J.,Kenya International Livestock Research Institute | Meyer B.,University of Bonn | Liljander A.,Kenya International Livestock Research Institute | And 8 more authors.
Emerging Infectious Diseases | Year: 2014

Dromedary camels are a putative source for human infections with Middle East respiratory syndrome coronavirus. We showed that camels sampled in different regions in Kenya during 1992-2013 have antibodies against this virus. High densities of camel populations correlated with increased seropositivity and might be a factor in predicting long-term virus maintenance. Source

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