The team screened human A549 (lung epithelial) cells infected with a modified influenza virus against the genome-wide siRNA library. Conducting two independent screens, they confirmed 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 antivirals. Protein interactions dataset analysis confirmed 181 host cellular factors that mediate 4,266 interactions between viral or cellular proteins.

Renate Koenig, Ph.D., of Burnham and Peter Palese, Ph.D., Silke Stertz, Ph.D., and Adolfo Garcia-Sastre, Ph.D., of Mount Sinai also collaborated on this research.

"Trying to identify all the host proteins that are required for the replication of influenza viruses is a wonderful challenge and we have come closer to 'knowing' all the genes involved," said Dr. Palese.

Dr. Young added, "These findings, combined with those from other RNAi screens, provide a blueprint of the cellular processes that are exploited more generally by viruses, pointing towards development of future broad-spectrum antiviral approaches."

Source: Burnham Institute for Medical Research