Influenza Virus Genome Even More Adaptable Than Thought

The influenza virus is quite dangerous because of its amazing inherent ability to mutate, thereby changing its properties and its pathogenicity -- which is the reason why new vaccines are neccessary on an annual basis for each new strain. European researchers have discovered that sequence variations in the virus genome alter virus pathogenicity not just by changing the viral proteins but by affecting the function of the virus genome itself, important knowledge that will be useful to fight future pandemic threats.

Given the ability to cross species barriers, new influenza virus types with different pathogenic properties might arise quickly. It is of paramount importance to quickly identify influenza viruses that are highly pathogenic or are efficiently transmitted between humans in the early stages of an epidemic.

An EU-funded research project, called 'Effect of natural viral RNA sequence variation on influenza virus RNA function' (RNAFLU), sought to investigate if mutations introduced in the influenza virus genome could affect the function of the viral RNA itself, regardless of the effect on the viral proteins. The working hypothesis was that such mutations might indirectly affect the ability of the virus to replicate in human cells, thereby affecting the pathogenic properties of the influenza virus or its ability to adapt to new host species.

In this context, researchers said they decided to investigate if naturally occurring mutations affected important properties and functions of the viral RNA, such as microRNA (mRNA) structure, splicing, binding to cellular mRNAs and mRNA translation. They found that RNA molecules derived from influenza viruses with different pathogenic properties or with different species tropism had different properties and secondary structure.

Additionally, well conserved binding sites for cellular mRNAs were identified in the influenza virus mRNAs that inhibited virus expression. Processing of the influenza viral mRNAs revealed substantial differences in splicing efficiencies, which might affect the ratio between proteins implicated in virus pathogenicity.

Collectively, RNAFLU results challenge the current perception that variation in influenza virus RNA sequence primarily affects viral proteins. The finding that differences in influenza RNA sequence affected the function of the RNA itself and impacted virus pathogenicity provides novel insight into the mechanisms of influenza virus pathogenicity. This knowledge could be employed for disease transmission control, minimising the chances of a flu pandemic.