Structure of human RIG-I bound to double-stranded RNA. Image: Joseph Marcotrigiano |
Researchers at Rutgers and UMDNJ-Robert Wood
Johnson Medical
School have determined the structure
of a protein that is the first line of defense in fighting viral infections
including influenza, hepatitis C, West Nile,
rabies, and measles.
Principal investigators of the
study, “Structural basis of RNA recognition and activation by innate
immune receptor RIG-I,” chosen for advanced online publication in Nature, say the research is key in
the development of broad-based drug therapies to combat viral infections.
“Understanding innate immunity to
viral infections is crucial to developing drugs that can fight viruses or
control inflammation,” says Joseph Marcotrigiano, assistant professor of chemistry and chemical biology at Rutgers who along
with Smita Patel, professor of biochemistry at Robert Wood Johnson Medical
School, are principal investigators on the newly released
study. “Having this foundation is extremely important.”
RIG-I is a receptor protein that
recognizes differences in molecular patterns in order to differentiate viral
RNA—the process during which virus particles makes new copies of themselves
within a host cell and can then infect other cells—from cellular RNA. What
researchers discovered is that viral RNA, as opposed to single-stranded
cellular RNA, is a double-stranded structure. This double-stranded difference
is the reason the RIG-I protein recognizes it and initiates a signal to induce
anti-immune and anti-inflammatory defenses within the cell.
Prior to this research, there was
little understanding on how RIG-I protein recognized the viral infections, says
Patel. Knowing. That it is due to the double-stranded molecular structure of
the viral RNA is critical because, he says, “a failure of RIG-I to
identify viral RNA can lead to alterations of the cell, including cell death,
inflammation, autoimmune diseases, and cancer.”
This is a first step, the
scientists say, in helping to develop therapies that interfere with a broad
variety of viral infections—a major breakthrough for millions of people who get
sick from viruses which cannot be treated effectively by current medication.
“This work provides unprecedented
insights on the molecular mechanism of viral RNA recognition by RIG-I,” says
Barbara Gerratana, who oversees enzyme catalysis grants at the National Institute of General Medical Sciences of
the National Institutes of Health. “As a
result, we have a deeper understanding of how the human body fights viral
infections and a structural basis of the development of new anti-viral
therapeutics.”
Filed Under: Drug Discovery
