ó Studies by a Carnegie Mellon University lab have shown
that some viruses violently expel their DNA inside human cells
when the virus reaches body temperature, and that it might be
possible to stop the spread of infection by interrupting that
by CMU biophysicist Alex Evilevitch and his team demonstrated
for the first time how the DNA packaged inside viruses shifts
from being stiffly inflexible to becoming loose and active
when the virus approaches 98.6 degrees.
study involving the herpes simplex virus, which affects
hundreds of millions of people worldwide, the researchers also
found that negative electrical charges in the viral DNA
accelerated its explosion into human cells.
studies raise the possibility that it might be possible to
treat viral infections by controlling this transition in the
mobility of viral DNA.
Iwasaki, an immunobiology researcher at the Yale School of
Medicine, who was not involved in the studies, said the
results suggest that "locking the viral DNA in the solid
state would be beneficial in the prevention of infection. If
we can find a virological agent that does that, it might be a
said his labís fundamental discoveries about viral
replication were made possible by sophisticated equipment,
including an atomic force microscope that uses a minuscule
needle to measure the surface features of viral DNA. Those
measurements allowed the lab to discover that before the virus
reaches body temperature, its DNA is still and inflexible.
first designing the research, about five years ago, Evilevitch
said his lab was hoping to discover something about
temperatureís role in the DNA transfer.
is rarely varied ... in most biophysical measurements in
viruses. Itís a new and rapidly developing field in
virology." New instruments are available and, he said,
"a lot of times studies were done on the virus, not the
single cell. We realized there were no studies on the
structure of DNA in viruses, very few, and those that are done
are done with cryo-electron microscopy and freezing the
said a better understanding of viruses was needed.
"Before we have a medical application in mind, first we
have to know how viruses work."
recently published two studies on their findings.
Proceedings of the National Academy of Sciences, the team
reported on their work with a virus that infects E. coli, a
bacteria that can cause severe diarrhea in people. This was
the one that found body temperature influenced the activity of
the DNA strands.
Nature Chemical Biology, the teamís study of herpes simplex
virus type 1 found that the similar solid-to-fluid DNA
transition also occurred at body temperature, and also was
linked to the ionic conditions (affecting electrical charges
and the mobility of DNA strands) in epithelial and neuronal
cells that are attacked by the herpes virus.
cells cover the inner and outer surfaces of the body and its
organs; neuronal cells are in the brain, spinal cord and
simplex virus is a challenge particularly for
immune-compromised patients, such as newborn babies and cancer
and HIV patients. Longtime use of antiviral medications can
lead to resistance. "Mutations develop faster in
immune-suppressed people," Evilevitch said.
virus lies latent in neuronal cells. "The neuronal cells
undergo wide variations of activity controlled by ion
concentration," he said. "We found that this affects
the state of the DNA in herpes capsid, affecting the ability
of the virus to release its DNA into the cell and its ability
to multiply." Virologist Fred Homa at the University of
Pittsburgh School of Medicine also participated in the study.
said although the antiviral drug Acyclovir is very effective
in treating herpes, "eventually the patient will develop
resistance to the drug."
herpes virus is challenging to get under control, agreed Yale
researcher Iwasaki. "Acyclovir doesnít cure the
disease. It just prevents the replication of the virus at the
time of the drug treatment. It needs to be continuously
added that, "Chipping away at any of these aspects of the
viral life cycle is important." Further research, she
said, might shed more light on how the virus expels the DNA
strands with an intense, rapid force into the host cell
might help us understand how the host might recognize, or
avoid the recognition, of the virus," she said.
"Perhaps this sort of ejection of the viral DNA might be
rejected by the host, somehow this might be recognized by the
innate immune system."