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Regions of importance for interaction of puumala virus nucleocapsid subunits
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
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2006 (English)In: Virus genes, ISSN 0920-8569, E-ISSN 1572-994X, Vol. 33, no 2, 169-174 p.Article in journal (Refereed) Published
Abstract [en]

Puumala virus (PUUV) is a hantavirus that causes a mild form of hemorrhagic fever with renal syndrome in northern and central Europe, and in large parts of Russia. The nucleocapsid (N) protein encoded by hantaviruses plays an important role in the life-cycle of these viruses, and one important function for the N-protein is to oligomerize, surround and protect the viral RNAs. We have identified amino- and carboxy-terminal regions involved in PUUV N-N interactions, which comprise amino acids 100-120 and 330-405. Our findings strengthen the hypothesis that the amino-terminus of the N-protein of hantaviruses holds a more regulatory function regarding N-N interactions, while conserved residues in the carboxy-terminal region, F335 together with F336 and W392, in concert with Y388 and/or F400 seems to play a more critical role in the PUUV N-N formation. This study provides evidence that the amino-terminal regions involved in the N-N interaction of Puumala virus are similar to those reported for Seoul virus (SEOV) and to some extent Hantaan virus (HTNV), even though the identity between PUUV N and SEOV/HTNV N is markedly lower than between PUUV N and Tula virus (TULV) N or Sin Nombre virus (SNV) N.

Place, publisher, year, edition, pages
2006. Vol. 33, no 2, 169-174 p.
Keyword [en]
Hantavirus, Nucleocapsid protein, Yeast two-hybrid, Protein–protein interactions, Puumala virus
National Category
Infectious Medicine
URN: urn:nbn:se:umu:diva-22246DOI: 10.1007/s11262-005-0045-5PubMedID: 16972031OAI: diva2:214133
Available from: 2009-05-04 Created: 2009-05-04 Last updated: 2013-01-30Bibliographically approved
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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