Identification of PTCH1 requirement for influenza virus using random homozygous gene perturbation

Wu Bo Li, Jie Zhu, Brit Hart, Baoquan Sui, Ke Weng, Shaojing Chang, Rebecca Geiger, Monserrat Torremorell, Alan Mileham, Christy Gladney, Martha A. Mellancamp, Limin Li, Abdul Yunus, Michael Goldblatt, Michael S. Kinch

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish
Pages (from-to)259-266
Number of pages8
JournalAmerican Journal of Translational Research
Volume1
Issue number3
StatePublished - Sep 18 2009
Externally publishedYes

Keywords

  • Influenza virus
  • PTCH1
  • Random homozygous gene perturbation (RHGP)
  • Resistance to therapies
  • SiRNA

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    Li, W. B., Zhu, J., Hart, B., Sui, B., Weng, K., Chang, S., Geiger, R., Torremorell, M., Mileham, A., Gladney, C., Mellancamp, M. A., Li, L., Yunus, A., Goldblatt, M., & Kinch, M. S. (2009). Identification of PTCH1 requirement for influenza virus using random homozygous gene perturbation. American Journal of Translational Research, 1(3), 259-266.