Virus-host cell interactions: implications for tropism, treatment, and targeting
Viral infections constitute a major burden to society and healthcare. Besides causing illness and death they also cause huge costs. Antibiotics function against bacterial infections but have no effect on viral infections. Vaccines and antiviral drugs are available for prevention and treatment of a few viral infections, but the vast majority of viral infections can neither be prevented by vaccines nor treated with antiviral drugs.
The main challenges with antiviral drug development is that viruses are relatively small in relation to e.g. bacteria, which means that there are fewer targets for treatment of viral infections. Viruses also replicate inside host cells, which means that antiviral drugs have to reach remote compartments of the cell to exert their effect
The main interest of our group is to explore the molecules and mechanisms involved in the early stage of the viral life cycle: attachment and entry. This is a critical step in the life cycle that sometimes determine the tropism of the virus, i.e. the cells, tissues and organs that are infected, but this step is also essential for subsequent replication and transmission to other cells and to other hosts. We also consider the importance of soluble molecules in surrounding body fluids, which may either prevent infection by serving as a barrier or as decoy receptors, but they may also function as a bridge to the target cells and thus facilitate infection.
Viruses are also used as tools, or ”vectors” in order to treat e.g. cancer and hereditary disorders, but also to prevent infections of heterologous pathogenes, i.e. as vaccine vectors. Our research is important to understand, and to improve the targeting of such vectors.
Hitherto, we have identified cellular receptors for different types of adenovirus and picornavirus. We have also developed an antiviral drug candidate for treatment of ocular adenoviruses, which have reached clinical trials.
To address the questions above we use advanced, 3D organoid cell models derived from primary cells and we also use transformed cell lines that correspond to the tropism of the virus. We use state-of-the-art technologies, including CRISPR/Cas9-engineered cells and viruses, surface plasmon resonance, advanced microcopy, and flow cytometry. We also collaborate with leading scientists in the areas of chemistry, structural biology, and glycobiology.
The current projects are funded mainly by grants from The European Union, The Swedish Research Council, The Swedish Cancer Society, and The Medical Faculty, Umeå University.