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Cross-reactive and serospecific epitopes of nucleocapsid proteins of three hantaviruses: prospects for new diagnostic tools.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
2008 (English)In: Virus Research, ISSN 0168-1702, Vol. 137, no 1, 97-105 p.Article in journal (Refereed) Published
Abstract [en]

The diagnosis of infectious diseases is sometimes difficult because of extensive immunological cross-reactivity between related viral antigens. On the path of constructing sero-specific antigens, we have identified residues involved in sero-specific and cross-reactive recognition of the nucleocapsid proteins (NPs) of Puumala virus (PUUV), Seoul virus (SEOV), and Sin Nombre virus (SNV) using serum samples from 17 Nephropathia epidemica patients. The mapping was performed by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis on a panel of N protein derivatives and alanine-substitution mutants in the three different hantavirus backgrounds. Four regions with different serological profiles were identified encompassing the amino acids (aa) 14-17, 22-24, 26, and 35-38. One of the regions showed strong cross-reactivity and was important for the recognition of SEOV and SNV antigens, but not the PUUV antigen (aa 35-38). Two regions displayed perceivable SEOV characteristics (aa 14-17 and aa 22-24 and 26) and the combined result of the alanine replacements resulted in a synergetic effect against the PUUV antigen (aa 14-17, 22-24, 26).

Place, publisher, year, edition, pages
2008. Vol. 137, no 1, 97-105 p.
Keyword [en]
Hantavirus; Puumala virus; Nucleocapsid protein; Human immune response; Cross-reactivity; Epitope mapping
URN: urn:nbn:se:umu:diva-22247DOI: 10.1016/j.virusres.2008.06.003PubMedID: 18620010OAI: diva2:214134
Available from: 2009-05-04 Created: 2009-05-04 Last updated: 2011-04-11
In thesis
1. Genetic and serologic characterization of a Swedish human hantavirus isolate
Open this publication in new window or tab >>Genetic and serologic characterization of a Swedish human hantavirus isolate
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hantaviruses are found practically all over the world and cause hemorrhagic fevers in man. Each year about 150,000 people are hospitalized in these zoonotic infections which can be of two types: hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS), depending on the infecting virus. Hantavirus infections are emerging infectious diseases. That is, the number of reported cases of hantaviral disease is increasing, new hantaviruses are discovered continually, and already known hantaviruses are expected to spread to new areas. Therefore, knowledge and monitoring of these viruses are imperative from a public health perspective.

In this thesis, the characterization of a local human Puumala (PUUV) virus isolate is described. Genetic and serological relationships to other hantaviruses are investigated and the viral protein interactions, critical for genome packaging and assembly, are studied. We found that the nucleotide and amino acid sequences of the local PUUV strains are significantly different from the PUUV prototype strain Sotkamo, a difference that indicates that there might be a risk of misdiagnosing PUUV infected patients when using reagents derived from the prototype strain. These data contributed to the introduction of locally derived diagnostic tools to the Laboratory of Clinical Virology at the Umeå University hospital, which is the reference centre for hantaviral diseases in Sweden. Furthermore, when studying the underlying mechanisms of genome packaging, we identified several regions and amino acids absolutely required for nucleocapsid protein interactions. Also, a region that appeared to regulate this interaction was discovered. Finally, the serological immune responses in DNA-vaccinated mice and PUUV infected patients were investigated. We found that the cross-reactive antibody response in vaccinated mice and in infected individuals was unique and independent of homologous titres. Furthermore, four immunodominant epitopes with specific cross-reactive characteristics were identified.

Our findings have highlighted the complexity of the serological immune responses to hantavirus infections, and they emphasize the importance of customizing the diagnostic tools and performing clinical analyses on locally derived strains. In conclusion, we believe that these results are valuable in the development of new serological, genetic, and epidemiological tools.

Place, publisher, year, edition, pages
Umeå: Infektionssjukdomar, 2008. 72 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1204
hantavirus, puumalavirus, diagnostics, HFRS, nucleocapsid protein, B-cell epitopes, epitope-mapping, protein interactions, glycosylation, antibody response, cross-reactivity
National Category
Microbiology in the medical area
urn:nbn:se:umu:diva-1878 (URN)978-91-7264-636-0 (ISBN)
Public defence
2008-10-24, Sal D, 1D, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Available from: 2008-10-10 Created: 2008-10-10 Last updated: 2009-05-04Bibliographically approved

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