'Staggering disease' is a neurological disease entity considered a threat to European domestic cats (Felis catus) for almost five decades. However, its aetiology has remained obscure. Rustrela virus ...(RusV), a relative of rubella virus, has recently been shown to be associated with encephalitis in a broad range of mammalian hosts. Here, we report the detection of RusV RNA and antigen by metagenomic sequencing, RT-qPCR, in-situ hybridization and immunohistochemistry in brain tissues of 27 out of 29 cats with non-suppurative meningoencephalomyelitis and clinical signs compatible with'staggering disease' from Sweden, Austria, and Germany, but not in non-affected control cats. Screening of possible reservoir hosts in Sweden revealed RusV infection in wood mice (Apodemus sylvaticus). Our work indicates that RusV is the long-sought cause of feline 'staggering disease'. Given its reported broad host spectrum and considerable geographic range, RusV may be the aetiological agent of neuropathologies in further mammals, possibly even including humans.
Rats are known as reservoirs and vectors for several zoonotic pathogens. However, information on the viruses shed by urban wild rats that could pose a zoonotic risk to human health is scare. Here, ...intestinal contents from 20 wild Norway rats (Rattus norvegicus) collected in the city of Berlin, Germany, were subjected to metagenomic analysis of viral nucleic acids. The determined faecal viromes of rats consisted of a variety of known and unknown viruses, and were highly variable among the individuals. Members of the families Parvoviridae and Picobirnaviridae represented the most abundant species. Novel picornaviruses, bocaviruses, sapoviruses and stool-associated circular ssDNA viruses were identified, which showed only low sequence identity to known representatives of the corresponding taxa. In addition, noroviruses and rotaviruses were detected as potential zoonotic gastroenteritis viruses. However, partial-genome sequence analyses indicated that the norovirus was closely related to the recently identified rat norovirus and the rotavirus B was closely related to the rat rotavirus strain IDIR; both viruses clustered separately from respective human virus strains in phylogenetic trees. In contrast, the rotavirus A sequences showed high identity to human and animal strains. Analysis of the nearly complete genome of this virus revealed the known genotypes G3, P3 and N2 for three of the genome segments, whereas the remaining eight genome segments represented the novel genotypes I20-R11-C11-M10-A22-T14-E18-H13. Our results indicated a high heterogeneity of enteric viruses present in urban wild rats; their ability to be transmitted to humans remains to be assessed in the future.
Epidemiologic surveillance of hepatitis E virus in over 300 free-ranging and captive cetaceans in waters off Spain revealed extensive exposure to this pathogen. We suggest the persistent and ...widespread presence of hepatitis E in the marine environment off the coast of Spain may be driven by terrestrial sources of contamination.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hantaviruses are predominantly rodent-borne pathogens, although recently novel shrew-associated hantaviruses were found. Within natural reservoir hosts, hantairuses do not cause obvious pathogenetic ...effects; transmission to humans, however, can lead to hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome, depending on the virus species involved. This review is focussed on the recent knowledge on hantavirus-induced immune responses in rodent reservoirs and humans and their impact on susceptibility, transmission, and outcome of hantavirus infections. In addition, this review incorporates a discussion on the potential role of direct cell-virus interactions in the pathogenesis of hantavirus infections in humans. Finally, questions for further research efforts on the immune responses in potential hantavirus reservoir hosts and humans are summarized.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Rotavirus A (RVA) is an etiologic agent of diarrhea in humans and animals. It shows a high degree of genetic heterogeneity. Although distinct associations of RVA genotypes with certain host species ...are common, interspecies-transmission has also been described. Recently, RVA strains, which are genetically distinct and cluster basally to all other RVA strains in phylogenetic trees, have been identified in common shrews (Sorex araneus). Here, the genome sequence analysis of another RVA strain (RVA/Common Shrew-wt/GER/KS11–0893/2010/G42P58) from a common shrew from Germany is described. Generally, the strain shows low sequence identities to established strains, which is reflected by the assessment of the novel genotypes G42-P58-I32-R28-C24-M24-A39-N28-T28-E32-H28 to its genome segments. Specifically, the strain is phylogenetically distant from previously described RVA strains of common shrews, whereas it is more closely related to other avian and mammalian RVA strains including those from Asian house shrews (Suncus murinus). The results indicate that a broad variety of diverse RVA strains can be found in shrews suggesting a significant role of these animals in rotavirus evolution.
•Genome sequencing of a new rotavirus A strain from a common shrew.•Novel genotypes have been assigned to all 11 genome segments.•Only distant relationship to previously determined common shrew strains.•Closer relationship to avian and mammalian strains.•Results indicate a broad variety of rotavirus A strains in shrews.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
(CPXV) is a zoonotic
(OPV) that infects a wide range of mammals. CPXV-specific DNA and antibodies were detected in different vole species, such as common voles (
) and bank voles (
). Therefore, ...voles are the putative main reservoir host of CPXV. However, CPXV was up to now only isolated from common voles. Here we report the detection and isolation of a bank vole-derived CPXV strain (GerMygEK 938/17) resulting from a large-scale screening of bank voles collected in Thuringia, Germany, during 2017 and 2018. Phylogenetic analysis using the complete viral genome sequence indicated a high similarity of the novel strain to CPXV clade 3 and to OPV "Abatino" but also to
(ECTV) strains. Phenotypic characterization of CPXV GerMygEK 938/17 using inoculation of embryonated chicken eggs displayed hemorrhagic pock lesions on the chorioallantoic membrane that are typical for CPXV but not for ECTV. CPXV GerMygEK 938/17 replicated in vole-derived kidney cell lines but at lower level than on Vero76 cell line. In conclusion, the first bank vole-derived CPXV isolate provides new insights into the genetic variability of CPXV in the putative reservoir host and is a valuable tool for further studies about CPXV-host interaction and molecular evolution of OPV.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Despite a growing knowledge about the biological diversity of papillomaviruses (PV), only little is known about non-human PV in general and about PV mice models in particular. We cloned and sequenced ...the complete genomes of two novel PV types from the Norway rat (Rattus norvegicus; RnPV2) and the wood mouse (Apodemus sylvaticus; AsPV1) as well as a novel variant of the recently described MmuPV1 (originally designated as MusPV) from a house mouse (Mus musculus; MmuPV1 variant). In addition, we conducted phylogenetic analyses using a systematically representative set of 79 PV types, including the novel sequences. As inferred from concatenated amino acid sequences of six proteins, MmuPV1 variant and AsPV1 nested within the Beta+Xi-PV super taxon as members of the Pi-PV. RnPV2 is a member of the Iota-PV that has a distant phylogenetic position from Pi-PV. The phylogenetic results support a complex scenario of PV diversification driven by different evolutionary forces including co-divergence with hosts and adaptive radiations to new environments. PV types particularly isolated from mice and rats are the basis for new animal models, which are valuable to study PV induced tumors and new treatment options.
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Hepatitis E virus (HEV) is the causative agent of an acute self-limiting hepatitis in humans. In industrialized countries, autochthonous cases are linked to zoonotic transmission from domestic pigs, ...wild boar and red deer. The main route of human infection presumably is consumption of contaminated meat. Farmers, slaughterers and veterinarians are expected to be risk groups as they work close to potentially infected animals. In this study, we tested four
Escherichia coli
-expressed segments of the capsid protein (CP) of a German wild boar-derived HEV genotype 3 strain for their diagnostic value in an indirect immunoglobulin G (IgG) ELISA. In an initial validation experiment, a carboxy-terminal CP segment spanning amino acid (aa) residues 326–608 outperformed the other segments harbouring aa residues 112–608, 326–660 and 112–335. Based on this segment, an indirect ELISA for detection of anti-HEV IgG antibodies in human sera was established and validated using a commercial line immunoassay as reference assay. A total of 563 sera from forestry workers of all forestry offices of Brandenburg, eastern Germany and 301 sera of blood donors from eastern Germany were surveyed using these assays. The commercial test revealed seroprevalence rates of 11% for blood donors and 18% for forestry workers. These rates are in line with data obtained by the in-house test (12 and 21%). Hence, the in-house test performed strikingly similar to the commercial test (sensitivity 0.9318, specificity 0.9542). An initial screening of forestry worker and blood donor sera with a corresponding CP segment of the recently discovered Norway rat-associated HEV revealed several strong positive sera exclusively in the forestry worker panel. Future investigations have to prove the performance of this novel IgG ELISA in large-scale seroepidemiological studies. In addition, the observed elevated seroprevalence in a forestry worker group has to be confirmed by studies on groups of forestry workers from other regions. The epidemiological role of ratHEV in human disease should be assessed in a large-scale study of risk and non-risk groups.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Rat hepatitis E virus (ratHEV) was detected in Norway and Black rats from Europe.•Nearly all novel sequences cluster in the proposed genotype 1 of ratHEV.•One sequence from Belgium clustered in a ...rabbit HEV-like genotype 3 clade.•No differences related to low and high density areas, age or sex were evident.
Rat hepatitis E virus (HEV) is genetically only distantly related to hepeviruses found in other mammalian reservoirs and in humans. It was initially detected in Norway rats (Rattus norvegicus) from Germany, and subsequently in rats from Vietnam, the USA, Indonesia, China, Denmark and France.
Here, we report on a molecular survey of Norway rats and Black rats (Rattus rattus) from 12 European countries for ratHEV and human pathogenic hepeviruses. RatHEV-specific real-time and conventional RT-PCR investigations revealed the presence of ratHEV in 63 of 508 (12.4%) rats at the majority of sites in 11 of 12 countries. In contrast, a real-time RT-PCR specific for human pathogenic HEV genotypes 1–4 and a nested broad-spectrum (NBS) RT-PCR with subsequent sequence determination did not detect any infections with these genotypes. Only in a single Norway rat from Belgium a rabbit HEV-like genotype 3 sequence was detected. Phylogenetic analysis indicated a clustering of all other novel Norway and Black rat-derived sequences with ratHEV sequences from Europe, the USA and a Black rat-derived sequence from Indonesia within the proposed ratHEV genotype 1. No difference in infection status was detected related to age, sex, rat species or density of human settlements and zoological gardens.
In conclusion, our investigation shows a broad geographical distribution of ratHEV in Norway and Black rats from Europe and its presence in all settlement types investigated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Hepatitis E virus (HEV) is a human pathogen with increasing importance. The lack of efficient cell culture systems hampers systematic studies on its replication cycle, virus neutralization and ...inactivation. Here, several cell lines were inoculated with the HEV genotype 3c strain 47832c, previously isolated from a chronically infected transplant patient. At 14 days after inoculation the highest HEV genome copy numbers were found in A549 cells, followed by PLC/PRF/5 cells, whereas HepG2/C3A, Huh-7 Lunet BLR and MRC-5 cells only weakly supported virus replication. Inoculation of A549-derived subclone cell lines resulted in most cases in reduced HEV replication. However, the subclone A549/D3 was susceptible to lower virus concentrations and resulted in higher virus yields as compared to parental A549 cells. Transcriptome analysis indicated a downregulation of genes for
(
)
and
, and an upregulation of the
(
) gene in A549/D3 cells compared to A549 cells. However, treatment of A549/D3 cells or A549 cells with CEACAM- or syndecan 2-specific antisera did not influence HEV replication. The results show that cells supporting more efficient HEV replication can be selected from the A549 cell line. The specific mechanisms responsible for the enhanced replication remain unknown.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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