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

American Journal of Translational Research

Michael Goldblatt¹  Martha A. Mellancamp¹  Shaojing Chang¹  Abdul Yunus¹  Rebecca Geiger¹  Limin Li¹  Montserrat Torremorell¹  Brit Hart¹  Alan Mileham¹  Jie Zhu¹  Ke Weng¹  Michael S. Kinch¹  Wu-Bo Li¹  Baoquan Sui¹  Christy Gladney¹ 

关键词: Influenza virus;    random homozygous gene perturbation (RHGP);    PTCH1;    resistance to therapies;    siRNA;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

Unknown