title: Identification of PTCH1 requirement for influenza virus using random homozygous gene perturbation.
abstract: Influenza infection remains a leading cause of infectious disease-mediated morbidity and mortality. Accumulating evidence indicates that most variants of seasonal and pandemic influenza have developed resistance to conventional therapies. Such information has spawned new interest in identifying novel approaches to target influenza. Our laboratories have been developing a new strategy of Host-Oriented Therapeutics, which seeks to target host molecules in a safe and effective manner that prevents the virus from causing disease. Using an improved discovery technology, Random Homozygous Gene Perturbation (RHGP), we identified the PTCH1 protein as an essential host target that critically controls influenza virus infection. We further demonstrated that targeted intervention against PTCH1 using antibodies or siRNA decreases influenza infection. Finally, we demonstrated the involvement of PTCH1 in influenza infection outside of the laboratory by showing that genetic variations of PTCH1 relate to decreased disease morbidity in the field. Altogether, these findings have important implications for the development of novel, host-directed therapeutics to improve influenza disease management.
authors: Wu-Bo
authors: WB
authors: Li
authors: Jie
authors: J
authors: Zhu
authors: Brit
authors: B
authors: Hart
authors: Baoquan
authors: B
authors: Sui
authors: Ke
authors: K
authors: Weng
authors: Shaojing
authors: S
authors: Chang
authors: Rebecca
authors: R
authors: Geiger
authors: Montserrat
authors: M
authors: Torremorell
authors: Alan
authors: A
authors: Mileham
authors: Christy
authors: C
authors: Gladney
authors: Martha A
authors: MA
authors: Mellancamp
authors: Limin
authors: L
authors: Li
authors: Abdul
authors: A
authors: Yunus
authors: Michael
authors: M
authors: Goldblatt
authors: Michael S
authors: MS
authors: Kinch