PROJECT SUMMARY: Influenza virus is a worldwide public health problem and has the potential to cause a pandemic. While vaccines can efficiently protect individuals from infection with influenza virus, there is still a great need for antiviral drugs that prevent disease progression and virus transmission. Thus, efforts are needed to study the influenza virus-host interactions, which are critical for developing novel drugs against the influenza virus, including broad-spectrum drugs. Like other viruses, influenza viruses depend on host cellular components to complete most steps of the viral life cycle. The long-term goal of this project is to identify the critical host cellular proteins that control influenza A virus replication, so that the information can be used for the development of new antiviral drugs. The NS1 protein of influenza virus is a major virulence factor that facilitates influenza virus replication through countering host antiviral response and regulating various processes in virus replication. The NS1 protein exerts these physiological functions largely through interacting with host cellular molecules. Through a quantitative proteomic method, it was recently found that the NS1 protein of influenza A virus interacts with DEAD-box protein 1 (DDX1), a putative DEAD-box-containing RNA helicase. Further preliminary studies demonstrate that knockdown of DDX1 dramatically reduces influenza A virus replication in human lung epithelial cells, suggesting that DDX1 protein is “hijacked” by influenza A virus and functions as a replication cofactor. Concomitantly, knockdown of DDX1 leads to significant decreases in interferon beta mRNA levels in influenza A virus infected cells, suggesting it plays an important role in regulating the transcription of type I interferons. Two specific aims will be pursued in this project. Aim 1. Examine the mechanism by which DDX1 facilitates influenza A virus replication. Aim 2. Examine the mechanisms by which DDX regulates interferon beta expression in influenza A virus-infected cells. The results will contribute to understanding the role of DDX1 in influenza A virus replication and enhance the understanding of influenza virus- host interactions. The results may shed light on designing novel strategies to control influenza viral infection.

PROJECT NARRATIVE: Influenza A viruses cause contagious respiratory illness and are responsible for periodic pandemics. The goal of this project is to investigate the role of an RNA helicase called DDX1 in influenza A virus replication and host antiviral response. The results may shed light on developing novel therapeutic strategies for controlling influenza A virus infection.