Senior Scholar Award in Global Infectious Disease
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.