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The envelope protei...
The envelope protein of tick-borne encephalitis virus influences neuron entry, pathogenicity, and vaccine protection
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- Lindquist, Richard, 1985- (författare)
- Umeå universitet,Avdelningen för virologi,Molekylär Infektionsmedicin, Sverige (MIMS)
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- Rosendal, Ebba (författare)
- Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Avdelningen för virologi
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- Weber, Elvira (författare)
- Umeå universitet,Avdelningen för virologi,Molekylär Infektionsmedicin, Sverige (MIMS)
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- Asghar, Naveed, 1983- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,School of Medical Sciences, Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, Örebro, Sweden
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- Schreier, Sarah (författare)
- Institute of Medical Microbiology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany; Innate Immunity and Infection, Helmholtz Centre for Infection Research, Braunschweig, Germany
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- Lenman, Annasara, 1983- (författare)
- Umeå universitet,Avdelningen för virologi,Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hannover, Germany
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- Johansson, Magnus, 1969- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,School of Medical Sciences, Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, Örebro, Sweden
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- Dobler, Gerhard (författare)
- Bundeswehr Institute of Microbiology, Munich, Germany
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- Bestehorn, Malena (författare)
- Bundeswehr Institute of Microbiology, Munich, Germany; Parasitology Unit, University of Hohenheim, D-, Stuttgart, Germany
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- Kröger, Andrea (författare)
- Institute of Medical Microbiology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany; Innate Immunity and Infection, Helmholtz Centre for Infection Research, Braunschweig, Germany
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- Överby, Anna K. (författare)
- Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Avdelningen för virologi
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(creator_code:org_t)
- 2020-09-28
- 2020
- Engelska.
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Ingår i: Journal of Neuroinflammation. - : BioMed Central. - 1742-2094. ; 17:1
- Relaterad länk:
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https://doi.org/10.1...
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https://jneuroinflam...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- BACKGROUND: Tick-borne encephalitis virus (TBEV) is considered to be the medically most important arthropod-borne virus in Europe. The symptoms of an infection range from subclinical to mild flu-like disease to lethal encephalitis. The exact determinants of disease severity are not known; however, the virulence of the strain as well as the immune status of the host are thought to be important factors for the outcome of the infection. Here we investigated virulence determinants in TBEV infection.METHOD: Mice were infected with different TBEV strains, and high virulent and low virulent TBEV strains were chosen. Sequence alignment identified differences that were cloned to generate chimera virus. The infection rate of the parental and chimeric virus were evaluated in primary mouse neurons, astrocytes, mouse embryonic fibroblasts, and in vivo. Neutralizing capacity of serum from individuals vaccinated with the FSME-IMMUN® and Encepur® or combined were evaluated.RESULTS: We identified a highly pathogenic and neurovirulent TBEV strain, 93/783. Using sequence analysis, we identified the envelope (E) protein of 93/783 as a potential virulence determinant and cloned it into the less pathogenic TBEV strain Torö. We found that the chimeric virus specifically infected primary neurons more efficiently compared to wild-type (WT) Torö and this correlated with enhanced pathogenicity and higher levels of viral RNA in vivo. The E protein is also the major target of neutralizing antibodies; thus, genetic variation in the E protein could influence the efficiency of the two available vaccines, FSME-IMMUN® and Encepur®. As TBEV vaccine breakthroughs have occurred in Europe, we chose to compare neutralizing capacity from individuals vaccinated with the two different vaccines or a combination of them. Our data suggest that the different vaccines do not perform equally well against the two Swedish strains.CONCLUSIONS: Our findings show that two amino acid substitutions of the E protein found in 93/783, A83T, and A463S enhanced Torö infection of neurons as well as pathogenesis and viral replication in vivo; furthermore, we found that genetic divergence from the vaccine strain resulted in lower neutralizing antibody titers in vaccinated individuals.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- Envelope protein
- European subtype
- Neurovirulence
- Pathogenesis
- Tick-borne encephalitis virus
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Lindquist, Richa ...
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Rosendal, Ebba
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Weber, Elvira
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Asghar, Naveed, ...
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Schreier, Sarah
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Lenman, Annasara ...
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Johansson, Magnu ...
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Dobler, Gerhard
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Bestehorn, Malen ...
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Kröger, Andrea
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Överby, Anna K.
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Örebro universitet
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Umeå universitet