Senior Scholar Award in Global Infectious Disease
Peter Cresswell, Ph.D.
Yale University School of Medicine

Antiviral Effects of Interferon-Inducible Cytosolic Proteins

It has been known for decades that a natural resistance mechanism for viral infections involves the production of interferons by infected cells. This family of antiviral molecules acts upon other cells to make them resistant to viral infection. Interferons induce the expression of a large number of molecules in the responding cells, but only a few have been functionally characterized and demonstrated to inhibit the infectious process. The goal of our research is to identify additional interferon-induced antiviral proteins and to determine their mechanisms of action.

Currently, our focus is on a family of cytoplasmic proteins known as guanylate binding proteins (GBP’s) which are cytoplasmic proteins. One of these, GBP1, has previously been shown to inhibit viral production and we have confirmed this. We have also shown that a second member of the family has similar antiviral properties. We are currently performing molecular studies to determine their mechanisms of action.

We have also identified a novel protein induced by interferons which has the property of inhibiting the production of human cytomegalovirus when stably expressed in cells prior to infection. Remarkably this protein is also induced by cytomegalovirus during a normal infection, arguing that the virus must have a method of avoiding the antiviral effect under these circumstances. Understanding these processes and the interaction of the novel protein with the cytomegalovirus replicative machinery may lead to possible novel antiviral therapies.

Contact Dr. Cresswell.