RNAFLU · EFFECT OF NATURAL VIRAL RNA SEQUENCE VARIATION ON INFLUENZA VIRUS RNA FUNCTION

Influenza A virus has an amazing ability to rapidly change its properties. We believe that pathogenic properties of an influenza virus could be determined also by differences in influenza virus RNA sequence that do not affect the protein sequence of the virus genome. In other words, sequences that affect structure and/or function of the viral RNA, could themselves contribute to the pathogenic properties of the influenza A virus, as well as its ability to adopt to a new host. All RNAs in a cell are associated with proteins and RNAs are dependent on these interactions to function efficiently. Interactions of RNA with proteins depend on the RNA sequence and secondary structure. The exact RNA sequence is therefore of paramount importance since it affects secondary structure and function and utilisation efficiencies of the viral RNAs. RNA sequence has a direct effect on mRNA splicing, mRNA stability and translation. The exact sequence of the influenza virus RNA should therefore affect the replication efficiency of each virus strain. It is reasonable to speculate that RNA sequence variation itself can affect virus pathogenic properties. The immediate goal of this short, 2-year project is therefore to investigate if naturally occurring RNA sequence variations in various influenza virus isolates with different pathogenic properties affect influenza virus RNA structure and function. The long-term goal with this project, which reaches past this 2-year period applied for here, is to determine if the influenza virus RNA sequence itself, independently of effects on viral protein sequence, affects viral pathogenesis and tropism.