Virological research work
The research work in the Department of Virology, Institute of Biomedicine is concentrating mainly on three significant areas of virology
1. Clinical virology and biotechnology. Viral diagnostic services carried out at the Department enable excellent collaborative possibilities for clinical virus research with hospitals and other health care units. Clinical virus research concentrates on the diagnostics of respiratory, gastrointestinal and neurological viral diseases. An essential question is to identify which viral pathogens are causing various clinical conditions. The diagnostic repertoire include up-to-date methods for detecting viruses and viral genetic materials and proteins (PCR, antigen detection and virus culture) and serological diagnostic procedures to identify immune responses against viruses. Special emphasis is being paid on studying childhood respiratory (rhinovirus, influenza and RSV infections) and gastrointestinal infections (enteroviruses), seroepidemiological analyses to estimate the disease burden in various population groups (e.g. children) and the causative agents of viral meningo-encephalitis (enteroviruses, Herpes group viruses). We also analyze the genetic and immunological characteristics of viruses in order to study molecular evolution and virulence determinants of important viral pathogens. In addition, we clone and express various viral genes in prokaryotic and eukaryotic expression vectors and use the purified recombinant proteins for diagnostic and research purposes. We also develop viral vectors (HSV) for enhancing their use e.g. in viral gene therapy and take part in developing fast, specific and cost effective microarray methods for detecting viral genetic materials and immune responses against the viruses. All research groups in the Department take part in clinical virus research and biotechnology.
2. Analysis of innate and adaptive immune responses in viral infections. Viral infections like other microbial infections induce immune responses in the host. Virus induced responses can be divided in rapidly activated innate immunity and more slowly developing virus-specific adaptive immune responses. Adaptive immune responses include humoral (B cell-dependent) and cell-mediated (T cell-dependent) immune responses. Our research unit is concentrating on mechanisms of activation of innate immunity in influenza, respiratory syncytial, hepatitis C and Herpes simplex virus infections. We intend to identify which of the pattern recognition receptor systems, Toll-like, Rig-I-like or NOD-like receptors (TLR, RLR or NLR, respectively) are operating in a given virus infection and how these receptor systems and what mechanisms are involved in the activation of intracellular signaling pathways. Our model systems include multiple stable cells lines and blood-derived human macrophages and dendritic cells (DCs). In addition, we analyze which of the innate immune mechanisms are contributing to antiviral resistance and what are the viral countermeasures to avoid the activation of innate immunity. Innate immunity is also regulating virus-specific humoral and cell-mediated immunity during natural infection and in response to vaccination. With the DC model system we intend to identify the factors contributing to DC activation and antigen presentation to T cells and how this process can be enhanced. In these studies we use the excellent confocal, live microscopic and proteomics core facilities provided by the University. In addition, our unit is taking part in analyzing the specificity, magnitude and persistence of immune responses induced by viral vaccines and natural viral infections. The groups lead by Drs. Julkunen, Hukkanen and Waris are working on understanding the details of viral immunity.
3. Virus – host cell interactions. Viruses are often using specific host cell molecules, receptors to enter the cells. Interaction of viruses with their host receptors leads to internalization of viruses and release of viral genetic material into the host cell cytoplasm or nucleus. Most RNA viruses replicate in the cytoplasm while DNA viruses and exceptionally also influenza virus replicates in the nucleus. Many viruses replicate only in specific cell or tissue types, which indicates that many viruses require host cell or tissue specific factors for their replication. The purpose of our research is to identify mechanisms how certain viruses are interacting with their receptors and what mechanisms are involved in virus entry (e.g. enteroviruses). The early steps of virus – host cell interactions are visualized by confocal and live microscopic techniques. In addition, we will identify factors and mechanisms regulating virus entry and cell activation at molecular and structural level. Another essential question is what host cell factors explain the ability of different viruses to replicate in specific types of host cells. Using host cell lines or primary cells originating from different tissues we characterize factors contributing to virus replication, virus growth kinetics, cell activation and apoptosis. The viral infections to be studied include enteroviruses and Herpes simplex viruses. The groups lead by Drs. Tauriainen, Susi and Hukkanen are carrying out this type of viral research work.