N protein as predictor of hantaviral virulence (pilot project)

The number of viruses identified in host species is growing and their pathogenic potential is mostly unknown. Members of the genus orthohantavirus belong to this group of emerging viruses. The genus comprises 58 members. However, only 22 members are described to be pathogenic and to cause renal or pulmonary failure. The other 36 members detected in host species are of unknown pathogenicity. There is no possibility to assess their virulence, because the knowledge on hantaviral pathogenesis is sparse and even close related members differ enormously in pathogenicity.

Therefore, an in vitro method to predict virulence of newly described hantaviruses would be of great interest. Our work identified hantaviral nucleocapsid protein (N protein) as pathogenicity factor. The expression of N protein in renal cells disturbs cell function by decreasing cellular motility and the extent of the effect is virus-specific: The impairment of migration capacity is more pronounced for the high-virulent Hantaan virus than for Puumala virus that causes a milder form of the disease.

Based on these results, analysis of N protein mediated effects on migration capacity would allow prediction of hantaviral virulence. Robust correlation between the intensity of motility impairment by N protein and pathogenicity is a prerequisite for the reliability of prediction. For that reason, we will examine the influence of N proteins derived from apathogenic hantaviruses and members with different pathogenicity on migration in vitro. If there is a correlation between motility impairment by N protein and virulence, the method would be suitable to estimate the risk potential of novel hantaviruses. In addition, the test method using expression of recombinant N Protein prevents working with potential infectious viruses. N protein as predictor of hantaviral virulence would be a useful tool in research and risk assessment in endemic regions.

Contact:

PD Dr. rer. nat. Ellen Krautkrämer
Sektion Nephrologie des Universitätsklinikums Heidelberg
Telefon: +49 6221 9112 222
ellen.krautkraemer@med.uni-heidelberg.de