We all know that a viral infection
can be developed extremely quickly, but in fact it's
even more dramatic than that - the process is literally
The pressure inside a virus
is 40 atmospheres, and it is just waiting for an opportunity
to blow up. The virus is like a living DNA cannon.
How this cannon functions has been mapped by Dr. Alex
Evilevitch at the Department of Biochemistry at Lund
University in Sweden. This is knowledge that will
have applications in gene therapy, drug development,
nanotechnology and the treatment of infections. This
involves a new type of virus research that is based
more on physics than biochemistry. Perhaps it could
be called virus biophysics. Alex Evilevitch took his
doctorate at Lund in physical chemistry and worked
for a few years at UCLA.
"There I met Professor
William Gelbart, who predicted on theoretical grounds
that the pressure in a bacteriophage - a virus that
attacks bacteria must be 40 atmospheres,"
explains Alex Evilevitch. "This roughly corresponds
to the pressure at a depth of 400 meters under the
sea. That's twenty times more than the pressure in
a car tire and ten times more than the pressure in
an unopened bottle of champagne. Using measurements,
I was able to confirm that Professor Gelbart's prediction
Evelevitch's research has attracted
considerable attention and landed him a prize for
the best research of the year in 2003 at UCLA and
a 2004 Chancellor's Award at the same university.
The list of recipients of the first prize includes
several scientists who went on to win a Nobel Prize.
But even though "virus biophysics" is a
hot research field in the U.S., Evilevitch chose to
return to Europe, where only a few research groups
pursue such research.
"It turns out that Lund
University has unique equipment for this research,"
says Alex Evilevitch. "At the National Center
for High-Resolution Electron Microscopy there is a
helium-cooled electron microscope. The cooling makes
it possible to examine sensitive biological material.
There are only a few electron microscopes like this
in the entire world, and I had the privilege to work
with it during the first months it was in regular
use in research. Right now I'm busy putting together
a research team in virus biophysics."
The virus that infects cells
in plants, animals, and humans penetrates in its entirety
into the cell and works inside. But bacteriophages
are viruses that attack bacteria, working from the
outside. The bacteriophage looks lik 20-faceted soccer
ball with a tail, or, perhaps rather a syringe needle.
It's only about 60 nanometers in size (one nanometer
= a billionth of a millimeter).
But its DNA, its genetic material,
is a strand that is about 17,000 nanometers long!
To get it into such a small body, everything has to
be packed tightly. What's more, the DNA has a negative
electrical charge, which makes the tangled up strands
repel each other.
When the bacteriophage comes
into contact with a certain type of receptor on the
surface of the bacteria cell, a canal in the tail
opens and its DNA violently rushes into the cell.
Once inside this DNA is reduplicated a million or
more times. At the same time new protein shells are
constructed for new virus particles. There is a special
molecular motor that acts like a screw in its threads,
rotating and pressing the DNA into the shell one bit
at a time, under rising pressure. It's the most powerful
molecular motor known.
Alex Evilevitch has continued
to publish his research findings after his return
to Lund. The latest (in Biophysical Journal, January
2005) contains measurements of the length of the DNA
strands that are propelled into the bacteria. An important
finding in that study is that it is a purely mechanical
force, not a chemical or biological process that is
at work when the virus DNA explodes.
At the moment Evilevitch is
developing methods to influence the mechanical packing
force in order to make it possible to squeeze more
DNA into the virus capsule.
"One method used today
for cloning a gene sequence is to insert it into bacteriophage
DNA," says Alex Evilevitch. "After the molecular
motor has worked this DNA into the virus capsule,
the virus is then allowed to infect a bacteria culture.
This in turn will produce millions of copies of the
alien DNA. This technique is limited by the fact that
there is only room for short sequences in the capsule.
If it proves to be possible to influence the force
needed to pack DNA, then that will enable even longer
DNA strands to be pressed in. That would be a significant
technological advance that would benefit future gene
therapy, cloning and the general development of molecular
Other ideas circulating in
this new scientific field involve the use of bacteriophages
as living syringe needles to inject drugs into cells.
The protein casing of bacteriophages, which is strong
enough to withstand the inner pressure, is also of
interest to scientists. In nanotechnology the search
is on for suitable packaging for carbon tubes and
other nanometer-size structures.
Perhaps protein shells will
provide the key to how sturdy containers can be constructed.
It is also plausible to use bacteriophages in treating
infected wounds, and in the U.S. trials are underway
to create safer foodstuffs by controlling bacterial
processes with bacteriophages.
Alex Evilevitch can be reached via e-mail at Alex.Evilevitch@biokem.lu.se