29 research outputs found
Association of low serum TGF-β level in hantavirus infected patients with severe disease
Background: Hantaviruses are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome, an immune-mediated pathogenesis is discussed. The aim of the present study was to investigate the role of TGF-β expression in acute hantavirus infection. Results: We retrospectively studied 77 patients hospitalised with acute Puumala infection during a hantavirus epidemic in Germany in 2012. Hantavirus infection was confirmed by positive anti-Puumala hantavirus IgG and IgM. Plasma levels of transforming growth factor (TGF)-β1 and TGF-β2 were analysed. Based on glomerular filtration rate on admission, patients were divided in mild and severe course of disease. Puumala virus RNA was detected by PCR amplification of the viral L segment gene. Out of 77 Puumala virus infected patients, 52 (68%) were male. A seasonal distribution was detected in our cohort with a peak in summer 2012, the highest incidence was observed in the age group of 30–39 years. Puumala virus RNA was detectable in 4/77 cases. Patients with severe disease had a significant longer hospital stay than patients with mild disease (6.2 vs 3.6 days). Thrombocyte count (186 vs 225 per nl), serum TGF-β1 (74 vs 118 ng/l) and TGF-β2 (479 vs 586 pg/l) were significantly lower in severe compared to mild disease. However, C-reactive protein (CRP) was significantly higher in patients with severe disease (62 vs 40 mg/l). TGF-β1/Cr was the most sensitive and specific marker associated with renal dysfunction. Conclusion: High serum CRP and low serum TGF-β in the early phase of hantavirus infection is associated with a severe course of disease. Our results support the hypothesis of an immune-mediated pathogenesis in hantavirus infection
Dobrava Hantavirus Infection Complicated by Panhypopituitarism, Istanbul, Turkey, 2010
We identified Dobrava-Belgrade virus infection in Turkey (from a strain related to hantavirus strains from nearby countries) in a patient who had severe symptoms leading to panhypopituitarism, but no known risk for hantavirus. Our findings emphasize the need for increased awareness of hantaviruses in the region and assessment of symptomatic persons without known risk factors for infection
Characterisation of the rat cytomegalovirus isolate "England"
Die beiden bislang im Wesentlichen untersuchten Isolate des Ratten-
Cytomegalovirus (RCMV) sind RCMV-Maastricht (RCMV M) und RCMV-England
(RCMV-E). Im Gegensatz zur veröffentlichten kompletten RCMV-M Sequenz wurden
von RCMV-E bislang Sequenzen nur partiell publiziert. Aufgrund der
Sequenzdaten und Unterschiede bezüglich ihrer Genomgröße und
Restriktionsmuster wurde angenommen, dass es sich bei den beiden Isolaten um
eigenständige Virusspezies handelt. Um dies zu bestätigen, wurden im Rahmen
dieser Arbeit die Leserahmen des RCMV-E Genoms identifiziert und mit RCMV-M
und dem murinen CMV (MCMV) verglichen. Sowohl im strukturellen Genomaufbau als
auch in den kodierten Genen weisen die Viren deutliche Unterschiede auf. Der
direkte Vergleich der Proteinsequenzen deutet auf eine nähere Verwandtschaft
des RCMV-E zu MCMV als zu RCMV-M hin. Anhand ausgewählter konservierter
Proteine wurden phylogenetische Analysen zur Eingruppierung des RCMV-E
innerhalb der CMVs durchgeführt. Diese Analysen belegen, dass es sich bei den
beiden Viren um distinkte Spezies handelt. Eine weitere Besonderheit des
RCMV-E besteht darin, eine Reihe von Genen zu kodieren, die bislang nicht in
anderen CMVs beschrieben wurden, zu welchen das RCMV C-Typ-Lektin-ähnliche
Protein (RCTL) gehört. In dieser Arbeit wurde RCTL funktionell untersucht.
Hierzu wurden zwei Rattenstämme mit RCMV-E Wildtypvirus und einer RCTL-
Deletionsmutante infiziert. Es konnte gezeigt werden, dass RCTL an den
inhibitorischen NK-Zell-Rezeptor NKR-P1B eines Rattenstammes bindet und die
Funktion des NK-Zell-Liganden rClr-b substituiert. Durch diese Interaktion
werden NK-Zellen nicht aktiviert und die infizierte Zelle vor NK-Zell-
mediierter Lyse geschützt. Hingegen führt der Verlust von RCTL zu einer
effizienten Eliminierung infizierter Zellen. Durch Depletion der NK-Zellen
kann dieser Verlust des RCTL kompensiert werden und die Deletionsmutante ist
wieder in der Lage, sich im Tier auszubreiten. In dem anderen Rattenstamm hat
der Verlust von RCTL keinen Einfluss auf die Ausbreitung des Virus in der
Ratte, so dass davon ausgegangen werden kann, dass nicht nur evolutionärer
Druck auf das Virus ausgeübt wird, sich dem Immunsystem zu entziehen, sondern
das Immunsystem auch einem Druck unterliegt, auf die Immunevasion des Erregers
zu reagieren.The two preponderant isolates of rat cytomegalovirus (RCMV) are RCMV-
Maastricht (RCMV-M) and RCMV-England (RCMV-E). In contrast to the completely
published RCMV-M sequence only partial sequence data of RCMV-E are available.
Based on this sequence data and differences in genome size and restriction
patterns, it has been assumed that both isolates represent independent virus
species. To verify this assumption, the open reading frames in RCMV-E were
identified and compared to those in RCMV-M and murine CMV (MCMV). Differences
among the viruses were observed in genome structure as well as in the encoded
genes. Direct comparison of the protein sequences revealed a closer
relationship between RCVM-E and MCMV than between RCMV-E and RCMV-M. Based on
a subset of conserved proteins, a phylogenetic analysis was performed to
classify the relationship of RCMV-E with other CMVs. This analysis proved that
RCMV-M and RCMV-E represent distinct species. Another characteristic aspect of
RCMV-E is that it encodes a couple of genes which have not been described in
other CMVs. One of those genes is the RCMV C-type-lectin-like protein (RCTL).
In this thesis, RCTL was functionally characterized. Therefore, two different
rat strains were infected with RCMV-E wildtyp virus and a RCTL deletion
mutant. It could be shown that RCTL binds to the inhibitory NK-cell receptor
NKR-P1B in one rat strain and functions as a decoy-ligand for the host NK-cell
ligand. By this interaction, NK-cell activation is silenced and the infected
cells are protected from NK-cell mediated lysis. In contrast, the loss of RCTL
results in an efficient elimination of the infected cells. By depleting the
NK-cells, the loss of RCTL can be compensated in that particular rat strain
and the virus is able to spread in the host. In the second rat strain, the
loss of RCTL as no effect on virus spread. Hence, it can be assumed that there
is not only an evolutionary pressure on the virus to evade the immune response
but also on the immune system to counteract the pathogen- associated immune
evasion mechanism
Cytomegalovirus Evasion of Innate Immunity by Subversion of the NKR-P1B:Clr-b Missing-Self Axis
SummaryCytomegaloviruses are known to encode several gene products that function to subvert MHC-dependent immune recognition. Here we characterize a rat cytomegalovirus (RCMV) C-type lectin-like (RCTL) gene product with homology to the Clr ligands for the NKR-P1 receptors. RCMV infection rapidly extinguished host Clr-b expression, thereby sensitizing infected cells to killing by natural killer (NK) cells. However, the RCTL protein functioned as a decoy ligand to protect infected cells from NK killing via direct interaction with the NKR-P1B inhibitory receptor. In vivo, an RCTL mutant virus displayed diminished virulence in an NK-dependent and strain-specific manner, suggesting that host NKR-P1 polymorphisms have evolved to avert the viral decoy mechanism while maintaining Clr-b recognition to preserve self tolerance. These findings reveal a unique strategy adopted by cytomegaloviruses to evade MHC-independent self-nonself discrimination. The existence of lectin-like genes in several poxviruses suggests that this may represent a common theme for viral evasion of innate immunity
Complete Genome Sequence of the English Isolate of Rat Cytomegalovirus (Murid Herpesvirus 8)
The complete genome of the English isolate of rat cytomegalovirus (RCMV-E) was determined. RCMV-E has a 202,946-bp genome with noninverting repeats but without terminal repeats. Thus, it differs significantly in size and genomic arrangement from closely related rodent cytomegaloviruses (CMVs). To account for the differences between the rat CMV isolates of Maastricht and England, RCMV-E was classified as Murid herpesvirus 8 by the International Committee on Taxonomy of Viruses
Multiple Synchronous Outbreaks of Puumala Virus, Germany, 2010
To investigate 2,017 cases of hantavirus disease in Germany, we compared 38 new patient-derived Puumala virus RNA sequences identified in 2010 with bank vole–derived small segment RNA sequences. The epidemic process was driven by outbreaks of 6 Puumala virus clades comprising strains of human and vole origin. Each clade corresponded to a different outbreak region