Genomic evolution of picornaviruses

​Description of Research

Picornaviruses are RNA viruses and therefore prone to rapid sequence evolution, which has resulted in almost three-hundred picornavirus types that have the capacity to infect human cells. Even though these viruses are the most common infectious agents in humans, there is no therapy against picornavirus disease and vaccines have been developed only against few picornavirus types. These are due to sequence variations, which affect viral gene functions and protein structures, and therefore play a central role in virus life cycle in cells and tissues.

In our research we focus on 1) virus evolution, which affects 2) tropism and pathogenicity in cell models and tissues, and 3) diagnostics. We are particularly interested in the relationship between virus evolution and cellular infectivity, i.e. natural sequence variation, which affects both virus binding to cell surface receptor(s) and virus replication (pathogenesis). We use NGS methods to analyze full-length picornavirus sequences and try to identify determinants that affect cellular infectivity. We are also developing both antigen and nucleic acid-based detection assays and therapy for picornaviruses. We use a panel of picornaviruses and picornavirus-derived proteins produced in heterologous hosts to develop serology and to generate pan-picorna monoclonal antibodies for point-of-care assay development. The same tools are used to select capsid binders (neutralizing human antibodies) from synthetic antibody libraries for use in therapy. Nucleic acid detection is based either on RT-qPCR, isothermal amplification or array methods, and used in routine diagnostics and for virus typing. Diagnostic tools aid in studies of virus life cycle - from receptor binding to entry and endocytosis into cells.

Selected Publications

Harvala et al. 2018. Recommendations for enterovirus diagnostics and characterization within and beyond Europe. J. Clin. Virol. 101, 11-17.

Hietanen et al. 2018. Genome sequences of RIGVIR oncolytic virotherapy virus and other echovirus 7 isolates. GenomeA 6: e00317-18.

Bruning et al.  2016. Detection and monitoring of human bocavirus 1 infection by a new rapid antigen test. New Microbes & New Infections. 11, 17-19.

Merilahti et al. 2016. Role of heparan sulfate in cellular infection of integrin-binding coxsackievirus A9 and human parechovirus 1 isolates. PLoS ONE 11(1): e147168.

Merilahti et al. 2016. Human parechovirus 1 infection occurs via aVb1 integrin. PLoS ONE 11(4): e0154769.

Ylä-Pelto et al. 2016. Therapeutic use of native and recombinant enteroviruses. Viruses 8, 57. 10.3390/v8030057.

Österback et al. 2014. Genome sequence of coxsackievirus A6, isolated during hand-foot-and-mouth disease outbreak in Finland in 2008. Genome Announcements 2, e01004-14.

Shakeel et al. 2013. Structural and functional analysis of coxsackievirus A9 integrin αVβ6 binding and uncoating. Journal of Virology 87, 3943–3951.

Heikkilä et al. 2011. A combined method for rescue of modified enteroviruses by mutagenic pri-mers, long PCR and T7 RNA polymerase-driven in vivo transcription. Journal of Virological Methods 171, 129-133.

Heikkilä et al. 2010. Endocytosis of coxsackievirus A9 via integrin αVβ6 and b2-microglobulin is mediated by dynamin and Arf6 but not caveolin1. Journal of Virology 84, 3666-3681.

Seitsonen et al. 2010. Interaction of αVβ3 and αVβ6 integrins with human parechovirus 1. Journal of Virology 84, 8509-8519.