Role of RNA helicase DDX1 in influenza A virus replication - 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.
