New technique to fight flu infection
EU-funded researchers have identified 287 human genes that the flu virus exploits when it infects us. Importantly, many of the genes are used by different strains of the influenza virus. Writing in the journal Nature, the researchers suggest that the virus would struggle to become resistant to drugs that block the action of these human genes.
EU support for the work came from the RIGHT ('RNA interference technology as human therapeutic tool') project, which is financed under the 'Life sciences, genomics and biotechnology for health' Thematic area of the Sixth Framework Programme (FP6), and the PATHOGENOMICS ('Trans-European cooperation and coordination of genome sequencing and functional genomics of human-pathogenic microorganisms') ERA-NET, which is funded under the 'Support for the coordination of activities' budget line of FP6.
Although the flu virus has genes of its own, it is unable to replicate without hijacking some of the genes of its host. Humans have some 24,000 genes, and the aim of this study was to determine which human genes the flu virus exploits during infection.
To do this, the scientists used a technique called RNA (ribonucleic acid) interference, or RNAi, to individually switch off every gene found in human cells. The cells were then infected with different strains of the influenza virus to determine the impacts of blocking each gene on the ability of the virus to replicate.
The experiments uncovered some 287 human genes that are involved in viral replication. Crucially, many of these genes are used by different strains of the influenza virus, including the ordinary H1N1 strain, the current pandemic H1N1 strain (also known as 'swine flu') and a highly pathogenic strain of bird flu (H5N1).
A major challenge facing those developing vaccines and drugs against flu is the ability of the virus to rapidly develop resistance to treatments. The fact that many of the genes identified are essential to a broad range of flu strains leads the researchers to suggest that the virus would be less likely to develop resistance to drugs targeting these genes.
The next step for the scientists is to investigate the newly discovered genes in depth and to eventually develop medicines designed to block their action without causing significant side effects. Once developed, these drugs would hopefully be effective against other, as yet unknown strains of influenza.
Just as they used RNAi to identify the human genes involved in flu infections, the researchers will also investigate whether RNAi could be used to treat the disease. Investigating the therapeutic potential of RNAi is a major aim of the EU-funded RIGHT project. The Max Planck Institute for Infection Biology in Germany, which led the research, is working with pharmaceutical companies to explore this option further.
'In the future, the strategy of switching off targeted genes at specific times will take on an important role in the fight against infectious diseases, alongside the application of antibiotics and vaccines,' commented RIGHT Project Coordinator Professor Thomas Meyer of the Max Planck Institute for Infection Biology. 'Although switching off human genes appears problematic at first, in fact it is exactly the same therapeutic principle that we have been successfully using for decades for the medical treatment of other diseases, from cancer to serious headaches. So why not for the treatment of infectious diseases?'
Category: Project results
Data Source Provider: Max Planck Society; Nature
Document Reference: Karlas, A. et al. (2010) Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature (in press), published online 17 January. DOI: 10.1038/nature08760.
Subject Index: Coordination, Cooperation; Life Sciences; Medicine, Health; Scientific Research