Scientists Discover How Energy Is
Released from a Virus During Infection
Within a virus's tiny exterior is a store of energy waiting to be
unleashed. When the virus encounters a host cell, this pent-up energy
is released, propelling the viral DNA into the cell and turning
it into a virus factory. For the first time, Carnegie Mellon University
physicist Alex Evilevitch has directly measured the energy associated
with the expulsion of viral DNA, a pivotal discovery toward fully
understanding the physical mechanisms that control viral infection
and designing drugs to interfere with the process.
"We are studying the physics of viruses, not the biology
of viruses," said Evilevitch, associate professor of physics
in the Mellon College of Science at Carnegie Mellon. "By
treating viruses as physical objects, we can identify physical
properties and mechanisms of infection that are common to a variety
of viruses, regardless of their biological makeup, which could
lead to the development of broad spectrum antiviral drugs."
Current antiviral medications are highly specialized. They target
molecules essential to the replication cycle of specific viruses,
such as HIV or influenza, limiting the drugs' use to specific
diseases. Additionally, viruses mutate over time and may become
less susceptible to the medication. Evilevitch's work in the burgeoning
field of physical virology stands to provide tools for the rational
design of less-specialized antiviral drugs that will have the
ability to treat a broad range of viruses by interrupting the
release of viral genomes into cells.
Evilevitch's current findings also have the potential to improve
the development of gene therapy, which uses viruses to deliver
functional genes directly to human cells to replace defective
genes that are causing disease. Gene therapy takes advantage of
viruses' modus operandi -- injecting genetic material into cells.
But instead of forcing in harmful, viral DNA, gene therapy delivers
helpful, functional genes. Controlled packaging of the functional
genes into the viral delivery system is one of the key factors
involved in developing a successful gene therapy.
Many viruses, whether they infect bacteria, plants or animals,
are adept at packing long stretches of nucleic acid (DNA or RNA)
within their nanometer-sized protein shells. In many of the viruses
that contain double-stranded DNA, the DNA gets packaged so tightly
that it bends upon itself, resulting in repulsive forces that
exert a tremendous amount of pressure on the virus's outer shell,
indicating a great amount of stored energy. At the moment of infection,
when the DNA is being shot out of the virus, the energy stored
in the tightly packed DNA is released and converted into thermal
Evilevitch and his colleagues from Lund University in Sweden,
where Evilevitch was previously employed, and the Universite de
Lyon in France used an experimental technique known as isothermal
titration calorimetry (ITC) to directly measure the heat, and
thus the thermal energy, released during viral genome ejection.
Until now, only indirect measurements of this energy have been
available. They describe this new method in the Feb. 5 issue of
the Journal of Molecular Biology.
"We are the first group to use titration calorimetry to
study genome release from viruses," Evilevitch said. "In
this study, we looked at viruses that infect bacteria, called
bacteriophages, as an experimental model system, but ITC can also
be applied to other types of viruses. We're currently investigating
the rotavirus, which causes stomach flu, using our new technique."
In the Journal of Molecular Biology report, Evilevitch used ITC
to measure the thermal energy released during genome ejection,
which is the same as the stored internal energy that results from
genome packaging. His results, which agree with analytical models
and computer simulations, show that the heat released increases
as DNA length increases. He also discovered that the ordering
of water molecules around DNA strands inside the virus (called
hydration entropy) has a tremendous influence on the build up
of energy. This unpredicted effect was not accounted for in the
"Understanding the energy profile for viral genome release
provides information on how to interfere with the process. For
example, developing ways to decrease the internal energy in viruses
could prevent viruses from ejecting their genome and prevent infection,"
February 8, 2010