London: An international team of scientists have made a novel discovery that might help explain how flu virus, including the currently circulating swine-origin H1N1 infects the body.
They have also identified small molecule compounds that act on several of these factors and inhibit viral replication, pointing to new ways to treat flu.
During the study, researchers have identified 295 human cell factors that influenza A strains must harness to infect a cell.
They used RNAi screening technology to selectively turn off more than 19,000 human genes to determine which human factors facilitate viral entry, uncoating, nuclear import, viral replication and other necessary functions of the virus.
"Because influenza mutates so readily, it has become a moving target for therapeutic intervention, making it difficult to treat circulating strains, including the H1N1 swine flu," Nature quoted researcher Sumit Chanda, from Burnham Institute for Medical Research.
"As a result, there is now widespread resistance to two classes of antiviral drugs. However, by targeting more stable human host factors, we may be able to develop therapies that prevent or treat a variety of influenza A strains and are more likely to maintain their effectiveness," Chanda added.
"This study has provided us with crucial knowledge of the cellular pathways and factors the influenza virus exploits to replicate," said co-researcher Megan Shaw, Ph.D., of Mount Sinai.
Each of these represents an ``Achilles heel`` of the virus and vastly increases the number of potential targets for new influenza antiviral drugs, Shaw added.
The team screened human A549 (lung epithelial) cells infected with a modified influenza virus against the genome-wide siRNA library.
The study showed that selectively impairing each of 295 cellular genes reduced viral infection, effectively illuminating the path followed by influenza viruses during the infection of a cell.
Importantly, they found that inhibiting proteins in known drug target classes, such as kinases, vATPases, and tubulin, impairs influenza growth, suggesting that small molecular weight compounds may be developed as host factor-directed anti-virals.
These findings were published online in the journal Nature.
ANI