Senior Scholar Award in Global Infectious Disease
Peter Palese, Ph.D.
Mount Sinai School of Medicine

Cellular Genes and Viruses: Who Wins The War?

Viruses can only replicate in live cells, and they rely on the host cell machinery for the amplification of their viral components. Because viral infection is usually detrimental to the host cell, the cell has evolved defense mechanisms which prevent replication of invading viruses. An intricate relationship exists between cellular defenses and viral counterattacks.

Our goal is to identify specific cellular genes or gene combinations that affect the outcome of infection by viruses. We will focus on lytic RNA viruses (with emphasis on influenza viruses), which have recently been shown to possess interferon-antagonist activities. Interferon is the primary component of the cell’s innate immune response, its first line of defense against an invading virus. Viral anti-interferon activities have a see-saw relationship with the innate immune (interferon) responses of the infected cell: when the viral attack is strong, the cell’s defenses are suppressed, and vice-versa. The outcome of this adversarial relationship determines the outcome of an infection.

We will establish screening protocols to identify cellular genes that possess antiviral (or proviral) activity by using either gene knock-out (via siRNA) or knock-in (via over-expression) conditions. These studies should help sort out, select and define the “important” genes involved in host-virus interactions. Such common genes/pathways may become important targets for antiviral interventions, resulting in the development of broad-range antivirals which are effective against more than one virus. Finally, we believe that identification of novel genes or gene combinations affecting the outcome of viral infection may help us correlate polymorphisms (mutations) in genes with genetic susceptibility to viral diseases.

Contact Dr. Palese.