An animal model for the tickborne flavivirus--Omsk hemorrhagic fever virus.
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The tickborne encephalitis (TBE) serocomplex of flaviviruses consists primarily of viruses that cause neurologic disease; these viruses include Omsk hemorrhagic fever virus (OHFV), a virus that is genetically related to other TBE serocomplex viruses but that circulates in an ecologically distinct niche and causes markedly different human disease. The objective of this study was to examine a potential small-animal model for OHFV and to compare the pathology of infection with that of the neurotropic tickborne flavivirus, Powassan virus (POWV). POWV-infected BALB/c mice demonstrated typical arboviral encephalitis, characterized by paresis and paralysis before death, and viral infection of the cerebrum, characterized by inflammation and necrosis. In contrast, lethal OHFV infection did not cause paralysis or significant infection of the cerebrum but showed marked involvement of the cerebellum. Distinct pathological results in the spleens suggest that the immune response in OHFV-infected mice is different from that in POWV-infected mice. This study demonstrates a clear pathological difference between OHFV-infected mice and POWV-infected mice and supports the use of the BALB/c mouse as a disease model for OHFV. (+info)
Severe tick borne encephalitis with simultaneous brain stem, bithalamic, and spinal cord involvement documented by MRI.
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A case of tick borne encephalitis (TBE) is reported, with simultaneous brain stem, spinal cord, and bilateral thalamic involvement confirmed by magnetic resonance imaging (MRI). After exposure to a TBE endemic region, the patient developed a biphasic clinical course with initial flu-like symptoms followed by a severe brain stem syndrome. The diagnosis of TBE was confirmed serologically. Repeated MRI scans showed brain stem, bithalamic, and spinal cord involvement. The outcome was favourable. TBE cases with concomitant myelitis tend to have a more severe clinical course and more likelihood of needing intensive care support. They should therefore be identified early in order to be prepared for life threatening respiratory complications. (+info)
First human cases of tickborne encephalitis, Norway.
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The first reported case of tickborne encephalitis (TBE) in Norway occurred in 1997. From 1997 to 2003, from zero to two cases of human TBE have been diagnosed per year in Norway, for a total of eight cases. Clinical TBE cases in dogs are not reported in Norway. (+info)
Concomitant tickborne encephalitis and human granulocytic ehrlichiosis.
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We report a patient with febrile illness and epidemiologic and clinical findings consistent with human granulocytic ehrlichiosis and tickborne encephalitis, in whom infection with Anaplasma phagocytophilum was demonstrated by polymerase chain reaction and seroconversion. Tickborne encephalitis virus infection was established by serum immunoglobulin (Ig) M and IgG antibodies. (+info)
Heterologous gene expression by infectious and replicon vectors derived from tick-borne encephalitis virus and direct comparison of this flavivirus system with an alphavirus replicon.
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The flavivirus tick-borne encephaltis virus (TBEV) was established as a vector system for heterologous gene expression. The variable region of the genomic 3' non-coding region was replaced by an expression cassette consisting of the reporter gene enhanced green fluorescent protein (EGFP) under the translational control of an internal ribosomal entry site element, both in the context of an infectious virus genome and of a replicon lacking the genes of the surface proteins prM/M and E. The expression level and the stability of expression were measured by fluorescence-activated cell-sorting analysis and compared to an established alphavirus replicon vector derived from Venezuelan equine encephaltis virus (VEEV), expressing EGFP under the control of its natural subgenomic promoter. On the first day, the alphavirus replicon exhibited an approximately 180-fold higher expression level than the flavivirus replicon, but this difference decreased to about 20- and 10-fold on days 2 and 3, respectively. Four to six days post-transfection, foreign gene expression by the VEEV replicon vanished almost completely, due to extensive cell killing. In contrast, in the case of the TBEV replicon, the percentage of positive cells and the amount of EGFP expression exhibited only a moderate decline over a time period of almost 4 weeks. The infectious TBEV vector expressed less EGFP than the TBEV replicon at all times. Significant expression from the infectious vector was maintained for four cell-culture passages. The results indicate that the VEEV vector is superior with respect to achieving high expression levels, but the TBEV system may be advantageous for applications that require a moderate, but more enduring, gene expression. (+info)
Differences in the postfusion conformations of full-length and truncated class II fusion protein E of tick-borne encephalitis virus.
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The trimeric postfusion structure of the C-terminally truncated fusion protein E of the flavivirus tick-borne encephalitis virus, a class II viral fusion protein, was previously determined (S. Bressanelli, K. Stiasny, S. L. Allison, E. A. Stura, S. Duquerroy, J. Lescar, F. X. Heinz, and F. A. Rey, EMBO J. 23:728-738, 2004). In this study we compared the properties of this truncated form with the full-length trimer and found that the so-called stem-anchor region not only confers additional stability to the full-length molecule but also structurally modifies the protein domain carrying the fusion peptide loop. These data provide experimental evidence to support the model of a fusion process that leads to the interaction of the stem-anchor region with the fusion peptide loop in the postfusion trimer. (+info)
Characterization of neutralizing antibodies to West Nile virus.
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We produced nine monoclonal antibodies (MAbs) directed against the West Nile virus E glycoprotein using three different immunization strategies: inactivated virus, naked DNA, and recombinant protein. Most of the MAbs bound to conformation dependent epitopes in domain III of the E protein. Four of the MAbs neutralized WNV infection and bound to the same region of domain III with high affinity. The neutralizing MAbs were obtained from mice immunized with inactivated virus alone or in combination with a DNA plasmid. In contrast, MAbs obtained by immunization with a soluble version of the E glycoprotein did not exhibit neutralizing activity. These non-neutralizing antibodies were cross-reactive with several other flaviviruses, including Saint Louis encephalitis, Japanese encephalitis, Yellow Fever and Powassan viruses. Interestingly, some non-neutralizing MAbs bound with high affinity to domains I or III, indicating that both affinity and the precise epitope recognized by an antibody are important determinants of WNV neutralization. (+info)
Combined prime-boost vaccination against tick-borne encephalitis (TBE) using a recombinant vaccinia virus and a bacterial plasmid both expressing TBE virus non-structural NS1 protein.
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BACKGROUND: Heterologous prime-boost immunization protocols using different gene expression systems have proven to be successful tools in protecting against various diseases in experimental animal models. The main reason for using this approach is to exploit the ability of expression cassettes to prime or boost the immune system in different ways during vaccination procedures. The purpose of the project was to study the ability of recombinant vaccinia virus (VV) and bacterial plasmid, both carrying the NS1 gene from tick-borne encephalitis (TBE) virus under the control of different promoters, to protect mice against lethal challenge using a heterologous prime-boost vaccination protocol. RESULTS: The heterologous prime-boost vaccination protocol, using a VV recombinant and bacterial plasmid, both containing the NS1 TBE virus protein gene under the control of different promoters, achieved a high level of protection in mice against lethal challenge with a highly pathogenic TBE virus strain. No signs of pronounced TBE infection were detected in the surviving animals. CONCLUSION: Heterologous prime-boost vaccination protocols using recombinant VV and bacterial plasmids could be used for the development of flavivirus vaccines. (+info)