The type I interferon (IFN) system represents one of the first-line defenses against viral infections. However, viral pathogens have evolutionarily acquired different exquisite mechanisms to counteract the IFN system of the host. Viral-encoded IFN antagonists have been identified among most groups of viruses. Since targeted deletion of the viral IFN antagonist genes results in viral attenuation, these genes represent major virulence factors. Human respiratory syncytial virus (RSV) is the leading cause of severe viral respiratory infections in infants and young children. Although recent evidence suggests that RSV infection results in inhibition of the antiviral action of IFN, little is known on the molecular mechanisms responsible for the RSV resistance to the IFN system. We have identified the NS2 protein of RSV as an RSV-encoded IFN antagonist based on its ability to restore the replication of an IFN-sensitive virus. In this part of the program project we will focus on the mechanism of evasion of the IFN system by RSV and its contribution to RSV replication, with special focus on the role of the NS2 protein. Through our studies, we will gain insights on the interactions between the NS2 protein of RSV and IFN-regulated pathways in the host. Such interactions might be good targets for antiviral and/or vaccine approaches against this important human pathogen.
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