The researchers focused on a protein called NS1, which is produced by the influenza virus. NS1 is known to bind to a human protein called hnRNP A1, but the details of this interaction and its role in the viral life cycle have been unclear.
Using a technique called X-ray crystallography, the researchers determined the atomic structure of the NS1-hnRNP A1 complex. This structure revealed that NS1 binds to a specific region of hnRNP A1, called the RRM2 domain. This interaction disrupts the normal function of hnRNP A1, which is involved in regulating gene expression.
The researchers also found that NS1 hijacks hnRNP A1 to help the virus replicate its RNA. NS1 recruits hnRNP A1 to the viral replication complex, where it helps to assemble the viral RNA into new virus particles.
This discovery provides a new understanding of how the influenza virus uses human proteins to replicate and infect other cells. It could lead to new treatments for viral infections by targeting the interaction between NS1 and hnRNP A1.
"Our findings provide a structural framework for understanding how NS1 hijacks hnRNP A1 to promote viral replication," said study lead author Dr. Christopher Basler, a professor of microbiology at UCSF. "This knowledge could be exploited to develop new antiviral therapies that target this interaction."
The research team is now working to develop small molecules that can block the interaction between NS1 and hnRNP A1. These molecules could be used to treat viral infections, including those caused by the influenza virus.
