Some viruses are evading our immune systems by blocking the protein
that our cells use as a “check” to block early stages of growth, thereby
allowing the deadly viruses to slip in unnoticed.
The blocking structure, called a “stem-loop,” is found at the beginning
of the virus’s genetic material. This discovery, recently published in the
, is the first time researchers
have found such an evasion mechanism built directly into the genetic material
of a virus.
|Credit: Fred Murphy, Sylvia Whitfield/CDC|
Scientists have discovered a defense system - built
into some viruses - that may be vulnerable to treatment.
The researchers studied alphaviruses similar to the Eastern
equine encephalitis virus, pictured above in red. This virus
is transmitted to humans and horses by mosquito bites.
“Knowing how viruses evade the immune system points to a potential
target for designing new drugs,” said co-author William Klimstra, Ph.D., associate
professor at the University of Pittsburgh’s
Center for Vaccine Research
. “One of the difficult parts of designing
antiviral drugs is making sure the drug targets the virus and not the host, or
the drug can cause some very serious side effects. It’s an especially tough nut
to crack, making this discovery a very productive area of investigation.”
Senior author Michael Diamond, M.D., Ph.D., a professor of medicine at
the Washington University School of Medicine in St. Louis, explained in a press release
changing a single letter of the virus’s genetic code scientists can disable the
stem-loop’s protective effects and allow the virus to be recognized by the host
“We hope to find ways to weaken the stem-loop structure with drugs or
other treatments, restoring the natural virus-fighting capabilities of the cell
and stopping or slowing some viral infections,” he said.
Dr. Klimstra and his colleagues at CVR did much of the virus work for
the research in Pitt’s Regional
, a unique, high-security facility constructed
with Pitt and NIH funds.
The researchers studied alphaviruses, a group of viruses that include
West Nile, influenza, SARS, yellow fever and polio. These viruses encode their
genes directly into RNA, which is genetic material read by a cell’s
When the alphavirus’s stem-loop is stable, a key immune system protein
called Ifit1 is blocked from binding to the viral RNA, allowing the virus to
begin growing in the cell and enabling infection to proceed unchecked. This
builds on several years of research by Dr. Klimstra’s team, including their 2005
discovery showing that Ifit1 has antiviral activity against invading RNA
“This built-in viral defense mechanism gives us a new opportunity to
improve treatment of infection,” said Dr. Diamond. “To control emergent infections,
we must continue to look for ways that viruses have antagonized our natural
defense mechanisms and discover how to disable them.”
Additional co-authors on this paper include Christina L. Gardener,
Ph.D., and Derek W. Trobaugh, Ph.D., both of Pitt’s CVR; Jennifer L. Hyde, Ph.D.,
James P. White, Ph.D., Gai Liu, Ph.D., and Gaya K. Amarasinghe, Ph.D., all of
Washington University; Taishi Kimura, and Kiyoshi Takeda, M.D., Ph.D., both of
Osaka University; Cheng Huang, Ph.D., and Slobodan Paessler, D.V.M., Ph.D., both
of the University of Texas.
Labels: University of Pittsburgh Center for Vaccine Research