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RNA viruses cause devastating infectious diseases, and new epidemics continue to emerge. We aim towards deep understanding of RNA virus replication at the molecular level. Through the discovery of basic mechanistic principles, we also hope to develop new and general antiviral strategies. We mainly work with alphaviruses, including Semliki Forest virus. The mosquito-borne alphaviruses can cause large outbreaks, as exemplified by the recent Chikungunya virus epidemic.

The replication of all positive-strand RNA viruses takes place in membrane-associated complexes in the cytoplasm of infected cells. The membrane probably plays organizing and supporting, as well as protecting and activating roles for the replication complex. The replication complex of alphaviruses and many related viruses is a membrane invagination of 50 nm in diameter. We have shown by electron microscopic tomography that each invagination is connected to the cytoplasm by a narrow neck structure. Thousands of active replication complexes are found on the inner surface of the plasma membrane and on the outer surface of endo-lysosomal vacuoles. The structure and formation of the replication complexes are studied by advanced electron microscopy and confocal microscopy methods.

We investigate the individual functional domains of the RNA replicase, including the capping enzyme, protease and the macro domain, which interacts with ADP-ribose derivatives. We also study other viruses, including hepatitis E virus and the infamous SARS coronavirus, for which we have discovered one of the RNA capping enzymes. In antiviral studies, we have developed automated screening methods utilizing marker genes inserted in the alphavirus genome. We have discovered antivirally active compounds, whose molecular mechanism of action is an interesting question.

I am involved in teaching biochemistry (especially metabolism), as well as virology and cell biology.

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