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Hantaviren in Deutschland
(2018)
Reil, Daniela ; Binder, Florian ; Freise, Jona ; Imholt, Christian ; Beyrers, Konrad ; Jacob, Jens ; Krüger, Detlev H. ; Hofmann, Jörg ; Dreesman, Johannes ; Ulrich, Rainer Günter
Hantaviren sind Kleinsäuger-assoziierte Krankheitserreger, die vor allem in Nagetieren, aber auch in Spitzmäusen, Maulwürfen und Fledermäusen vorkommen. Ziel dieser Arbeit ist es, einen aktuellen Überblick zur Epidemiologie und Ökologie der Hantaviren in Deutschland zu geben und Modelle zur Vorhersage von Virusausbrüchen zu diskutieren. In Deutschland werden die meisten humanen Erkrankungsfälle beim Menschen durch das von der Rötelmaus (Myodes glareolus) übertragene Puumalavirus (PUUV) verursacht. PUUV ist mit der westlichen evolutionären Linie der Rötelmaus assoziiert und fehlt im östlichen und nördlichen Teil Deutschlands. Ein zweites humanpathogenes Hantavirus ist das Dobrava-Belgrad-Virus (DOBV), Genotyp Kurkino, dessen Reservoir die vor allem im östlichen Teil Deutschlands vorkommende Brandmaus (Apodemus agrarius) ist. Ein PUUV-verwandtes Hantavirus ist das selten humanpathogene Tulavirus (TULV), das mit der Feldmaus (Microtus arvalis) assoziiert ist. Darüber hinaus wurden mit dem Seewis-, Asikkala- und Brugesvirus Spitzmaus- und Maulwurf-assoziierte Hantaviren mit noch unklarer Humanpathogenität gefunden.
Die humanen Erkrankungen sind jeweils mit den verschiedenen Hantaviren in deren regionaler Verteilung assoziiert und können mild bis schwer, aber auch subklinisch verlaufen. Das Auftreten von Häufungen humaner, durch PUUV verursachter Erkrankungen in den Jahren 2007, 2010, 2012, 2015 und 2017 korreliert mit dem Auftreten einer starken Fruktifikation der Buche („Buchenmast“) im jeweiligen Vorjahr. Auf der Basis von Wetterparametern sind Modelle zur Vorhersage von PUUV-Erkrankungshäufungen entwickelt worden, die zukünftig validiert und optimiert werden müssen. Neben dem Ausmaß des Virusvorkommens im Reservoir wird das Risiko humaner Infektionen durch das Expositionsverhalten des Menschen beeinflusst. Durch die Anwendung von Prognosemodellen soll der öffentliche Gesundheitsdienst in die Lage versetzt werden, räumlich und zeitlich gezielte und sachgerechte Präventionsempfehlungen für die Bevölkerung abzugeben.
Heg1 and Ccm1/2 proteins control endocardial mechanosensitivity during zebrafish valvulogenesis
(2018)
Donat, Stefan ; Lourenco, Marta Sofia Rocha ; Paolini, Alessio ; Otten, Cecile ; Renz, Marc ; Abdelilah-Seyfried, Salim
Endothelial cells respond to different levels of fluid shear stress through adaptations of their mechanosensitivity. Currently, we lack a good understanding of how this contributes to sculpting of the cardiovascular system. Cerebral cavernous malformation (CCM) is an inherited vascular disease that occurs when a second somatic mutation causes a loss of CCM1/KRIT1, CCM2, or CCM3 proteins. Here, we demonstrate that zebrafish Krit1 regulates the formation of cardiac valves. Expression of heg1, which encodes a binding partner of Krit1, is positively regulated by blood-flow. In turn, Heg1 stabilizes levels of Krit1 protein, and both Heg1 and Krit1 dampen expression levels of klf2a, a major mechanosensitive gene. Conversely, loss of Krit1 results in increased expression of klf2a and notch1b throughout the endocardium and prevents cardiac valve leaflet formation. Hence, the correct balance of blood-flow-dependent induction and Krit1 protein mediated repression of klf2a and notch1b ultimately shapes cardiac valve leaflet morphology.
Ryll, Rene ; Eiden, Martin ; Heuser, Elisa ; Weinhardt, Markus ; Ziege, Madlen ; Hoeper, Dirk ; Groschup, Martin H. ; Heckel, Gerald ; Johne, Reimar ; Ulrich, Rainer G.
Rabbit associated genotype 3 hepatitis E virus (HEV) strains were detected in feral, pet and farm rabbits in different parts of the world since 2009 and recently also in human patients. Here, we report a serological and molecular survey on 72 feral rabbits, collected along a rural-urban transect in and next to Frankfurt am Main, Central Germany. ELISA investigations revealed in 25 of 72 (34.7%) animals HEV-specific antibodies. HEV derived RNA was detected in 18 of 72 (25%) animals by reverse transcription-polymerase chain reaction assay. The complete genomes from two rabbitHEV-strains, one from a rural site and the other from an inner-city area, were generated by a combination of high-throughput sequencing, a primer walking approach and 5′- and 3′- rapid amplification of cDNA ends. Phylogenetic analysis of open reading frame (ORF)1-derived partial and complete ORF1/ORF2 concatenated coding sequences indicated their similarity to rabbit-associated HEV strains. The partial sequences revealed one cluster of closely-related rabbitHEV sequences from the urban trapping sites that is well separated from several clusters representing rabbitHEV sequences from rural trapping sites. The complete genome sequences of the two novel strains indicated similarities of 75.6–86.4% to the other 17 rabbitHEV sequences; the amino acid sequence identity of the concatenated ORF1/ORF2-encoded proteins reached 89.0–93.1%. The detection of rabbitHEV in an inner-city area with a high human population density suggests a high risk of potential human infection with the zoonotic rabbitHEV, either by direct or indirect contact with infected animals. Therefore, future investigations on the occurrence and frequency of human infections with rabbitHEV are warranted in populations with different contact to rabbits.
Kruse, Stefan ; Epp, Laura Saskia ; Wieczorek, Mareike ; Pestryakova, Luidmila Agafyevna ; Stoof-Leichsenring, Kathleen Rosemarie ; Herzschuh, Ulrike
Arctic treelines are facing a strong temperature increase as a result of recent global warming, causing possible changes in forest extent, which will alter vegetation-climate feedbacks. However, the mode and strength of the response is rather unclear, as potential changes are happening in areas that are very remote and difficult to access, and empirical data are still largely lacking. Here, we assessed the current population structure and genetic differentiation of Larix Mill. tree stands within the northernmost latitudinal treeline reaching ~ 72° N in the southern lowlands of the Taymyr Peninsula (~ 100° E). We sampled 743 individuals belonging to different height classes (seedlings, saplings, trees) at 11 locations along a gradient from ‘single tree’ tundra over ‘forest line’ to ‘dense forest’ stands and conducted investigations applying eight highly polymorphic nuclear microsatellites. Results suggest a high diversity within sub-populations (HE = 0.826–0.893), coupled, however, with heterozygote deficits in all sub-populations, but pronounced in ‘forest line’ stands. Overall, genetic differentiation of sub-populations is low (FST = 0.005), indicating a region-wide high gene flow, although ‘forest line’ stands harbour few rare and private alleles, likely indicating greater local reproduction. ‘Single tree’ stands, located beyond the northern forest line, are currently not involved in treeline expansion, but show signs of a long-term refuge, namely asexual reproduction and change of growth-form from erect to creeping growth, possibly having persisted for thousands of years. The lack of differentiation between the sub-populations points to a sufficiently high dispersal potential, and thus a rapid northward migration of the Siberian arctic treeline under recent global warming seems potentially unconstrained, but observations show it to be unexpectedly slow.
Fischer, Stefan ; Spierling, Nastasja G. ; Heuser, Elisa ; Kling, Christopher ; Schmidt, Sabrina ; Rosenfeld, Ulrike ; Reil, Daniela ; Imholt, Christian ; Jacob, Jens ; Ulrich, Rainer G. ; Essbauer, Sandra
Since the beginning of the 21st century, spotted fever rickettsioses are known as emerging diseases worldwide. Rickettsiae are obligately intracellular bacteria transmitted by arthropod vectors. The ecology of Rickettsia species has not been investigated in detail, but small mammals are considered to play a role as reservoirs. Aim of this study was to monitor rickettsiae in wild small mammals over a period of five years in four federal states of Germany. Initial screening of ear pinna tissues of 3939 animals by Pan-Rick real-time PCR targeting the citrate synthase (gltA) gene revealed 296 rodents of seven species and 19 shrews of two species positive for rickettsial DNA. Outer membrane protein gene (ompB, ompAIV) PCRs based typing resulted in the identification of three species: Rickettsia helvetica (90.9%) was found as the dominantly occurring species in the four investigated federal states, but Rickettsia felis (7.8%) and Rickettsia raoultii (1.3%) were also detected. The prevalence of Rickettsia spp. in rodents of the genus Apodemus was found to be higher (approximately 14%) than in all other rodent and shrew species at all investigated sites. General linear mixed model analyses indicated that heavier (older) individuals of yellow-necked mice and male common voles seem to contain more often rickettsial DNA than younger ones. Furthermore, rodents generally collected in forests in summer and autumn more often carried rickettsial DNA. In conclusion, this study indicated a high prevalence of R. helvetica in small mammal populations and suggests an age-dependent increase of the DNA prevalence in some of the species and in animals originating from forest habitats. The finding of R. helvetica and R. felis DNA in multiple small mammal species may indicate frequent trans-species transmission by feeding of vectors on different species. Further investigations should target the reason for the discrepancy between the high rickettsial DNA prevalence in rodents and the so far almost absence of clinical apparent human infections.
Autenrieth, Marijke ; Hartmann, Stefanie ; Lah, Ljerka ; Roos, Anna ; Dennis, Alice B. ; Tiedemann, Ralph
The harbour porpoise (Phocoena phocoena) is a highly mobile cetacean found across the Northern hemisphere. It occurs in coastal waters and inhabits basins that vary broadly in salinity, temperature and food availability. These diverse habitats could drive subtle differentiation among populations, but examination of this would be best conducted with a robust reference genome. Here, we report the first harbour porpoise genome, assembled de novo from an individual originating in the Kattegat Sea (Sweden). The genome is one of the most complete cetacean genomes currently available, with a total size of 2.39 Gb and 50% of the total length found in just 34 scaffolds. Using 122 of the longest scaffolds, we were able to show high levels of synteny with the genome of the domestic cattle (Bos taurus). Our draft annotation comprises 22,154 predicted genes, which we further annotated through matches to the NCBI nucleotide database, GO categorization and motif prediction. Within the predicted genes, we have confirmed the presence of >20 genes or gene families that have been associated with adaptive evolution in other cetaceans. Overall, this genome assembly and draft annotation represent a crucial addition to the genomic resources currently available for the study of porpoises and Phocoenidae evolution, phylogeny and conservation.
In this study we compared the phylogeographic patterns of two Rusa species, Rusa unicolor and Rusa timorensis, in order to understand what drove and maintained differentiation between these two geographically and genetically close species and investigated the route of introduction of individuals to the islands outside of the Sunda Shelf. We analyzed full mitogenomes from 56 archival samples from the distribution areas of the two species and 18 microsatellite loci in a subset of 16 individuals to generate the phylogeographic patterns of both species. Bayesian inference with fossil calibration was used to estimate the age of each species and major divergence events. Our results indicated that the split between the two species took place during the Pleistocene, similar to 1.8Mya, possibly driven by adaptations of R. timorensis to the drier climate found on Java compared to the other islands of Sundaland. Although both markers identified two well-differentiated clades, there was a largely discrepant pattern between mitochondrial and nuclear markers. While nDNA separated the individuals into the two species, largely in agreement with their museum label, mtDNA revealed that all R. timorensis sampled to the east of the Sunda shelf carried haplotypes from R. unicolor and one Rusa unicolor from South Sumatra carried a R. timorensis haplotype. Our results show that hybridization occurred between these two sister species in Sundaland during the Late Pleistocene and resulted in human-mediated introduction of hybrid descendants in all islands outside Sundaland.
Historical biogeography of the leopard (Panthera pardus) and its extinct Eurasian populations
(2018)
Paijmans, Johanna L. A. ; Barlow, Axel ; Förster, Daniel W. ; Henneberger, Kirstin ; Meyer, Matthias ; Nickel, Birgit ; Nagel, Doris ; Worsøe Havmøller, Rasmus ; Baryshnikov, Gennady F. ; Joger, Ulrich ; Rosendahl, Wilfried ; Hofreiter, Michael
Background
Resolving the historical biogeography of the leopard (Panthera pardus) is a complex issue, because patterns inferred from fossils and from molecular data lack congruence. Fossil evidence supports an African origin, and suggests that leopards were already present in Eurasia during the Early Pleistocene. Analysis of DNA sequences however, suggests a more recent, Middle Pleistocene shared ancestry of Asian and African leopards. These contrasting patterns led researchers to propose a two-stage hypothesis of leopard dispersal out of Africa: an initial Early Pleistocene colonisation of Asia and a subsequent replacement by a second colonisation wave during the Middle Pleistocene. The status of Late Pleistocene European leopards within this scenario is unclear: were these populations remnants of the first dispersal, or do the last surviving European leopards share more recent ancestry with their African counterparts?
Results
In this study, we generate and analyse mitogenome sequences from historical samples that span the entire modern leopard distribution, as well as from Late Pleistocene remains. We find a deep bifurcation between African and Eurasian mitochondrial lineages (~ 710 Ka), with the European ancient samples as sister to all Asian lineages (~ 483 Ka). The modern and historical mainland Asian lineages share a relatively recent common ancestor (~ 122 Ka), and we find one Javan sample nested within these.
Conclusions
The phylogenetic placement of the ancient European leopard as sister group to Asian leopards suggests that these populations originate from the same out-of-Africa dispersal which founded the Asian lineages. The coalescence time found for the mitochondrial lineages aligns well with the earliest undisputed fossils in Eurasia, and thus encourages a re-evaluation of the identification of the much older putative leopard fossils from the region. The relatively recent ancestry of all mainland Asian leopard lineages suggests that these populations underwent a severe population bottleneck during the Pleistocene. Finally, although only based on a single sample, the unexpected phylogenetic placement of the Javan leopard could be interpreted as evidence for exchange of mitochondrial lineages between Java and mainland Asia, calling for further investigation into the evolutionary history of this subspecies.
Genetic studies of the Eurasian brown bear (Ursus arctos) have so far focused on populations from Europe and North America, although the largest distribution area of brown bears is in Asia. In this study, we reveal population genetic parameters for the brown bear population inhabiting the Grand Kackar Mountains (GKM) in the north east of Turkey, western Lesser Caucasus. Using both hair (N = 147) and tissue samples (N = 7) collected between 2008 and 2014, we found substantial levels of genetic variation (10 microsatellite loci). Bear samples (hair) taken from rubbing trees worked better for genotyping than those from power poles, regardless of the year collected. Genotyping also revealed that bears moved between habitat patches, despite ongoing massive habitat alterations and the creation of large water reservoirs. This population has the potential to serve as a genetic reserve for future reintroduction in the Middle East. Due to the importance of the GKM population for on-going and future conservation actions, the impacts of habitat alterations in the region ought to be minimized; e.g., by establishing green bridges or corridors over reservoirs and major roads to maintain habitat connectivity and gene flow among populations in the Lesser Caucasus.