For those of you who read and remember my last blog post you
will be familiar with the gigantic mimivirus. Mimivirus was discovered as a
virus and not a bacterium back in 2003 by a team who subsequently went on to
find a very closely related virus which they termed mamavirus owing to the fact
that it is slightly larger than mimi. Once again the sheer size of this virus
was somewhat astounding and more importantly the fact that a second giant was
found makes it seem more likely that there may be more. But what was really
interesting about mamavirus is that when it was first isolated it was done so
with another virus in tow.
 | |||||
| Sputnik inside mamavirus - from origional Nature paper on Sputnik |
Mamavirus is roughly the same size as mimivirus, around
750nm in diameter as I described in the previous blog. However, a virus of much
more classical size at 50nm was also seen under the electron microscope. This
virus was named Sputnik in honour of the first man-made satellite as it was
seen to be a satellite to the much larger mamavirus. Satellite viruses are not
a new phenomenon, others have been observed, and at first Sputnik was thought
to simply behave like the other satellite viruses in that it would infect its
host (in this case an amoeba) at the same time as the larger virus and
replicate itself in the host with help from the other virus. However, this was
shown not to be the case - Sputnik actually infects mamavirus!
When mamavirus infects its amoeba host it sets up “viral
factories” in the cell where it can replicate its genetic material and make
many new copies of itself; the term factory is highly fitting for this process
as hundreds upon thousands of new viruses are turned out from these factories,
allowing spread of the virus. After it was observed that Sputnik could only
grow in the amoeba when mamavirus was simultaneously present, it was seen that
the smaller virus actually hijacks these viral factories and uses them for its
own replication, to the detriment of mamavirus. Mamavirus as a result becomes
unable to replicate itself efficiently and, for want of a better term, becomes sick.
Owing to its parasitic actions on mamavirus, Sputnik was coined a virophage (or
virus eater).
Before Sputnik, no virus had ever been seen to directly
cause damage to another virus, yet a virus infecting a bacterium is not a new
idea and was first observed as early as 1915 and 1917, in independent works.
These viruses that infect bacteria are known as bacteriophage, hence the logic
behind the naming of virophage. I bring bacteria into the story, as one of the
exciting aspects of mimi and mama is that they have begun to blur the lines
between living organisms and the viruses (again refer back to the previous
post). The discovery of smaller viruses that can infect these large viruses
further emphasises the idea that they may be on the very cusp of being classed
as alive.
Now for something exciting regarding virophage on a somewhat
more practical level. I’m sure most people are well aware of the current
problem we face with regard to bacterial infections. Back in 1928 when
Alexander Fleming somewhat fortuitously discovered penicillin, he launched what
has become commonly known as our arms race with bacteria. We are constantly
producing antibiotics to limit the burden of infection from bacteria. Yet the
bacteria don’t just sit back and let us kill them; they themselves are
constantly looking to survive and grow, and as a result they develop protection
against our interventions. We develop new antibiotics, the bacteria develop new
protections and so on. This evolutionary back and forth can often lead to a steady
state where neither has the advantage over the other, which has been termed the
Red Queen hypothesis, after the Red Queen in Alice in Wonderland (“It takes all
the running you can do to stay in one place…”). However at the present time bacteria
seem to have a slight edge over us in this arms race with strains such as MRSA
and multidrug resistant tuberculosis becoming ever more common, and the
development of new antibiotics slowing down. As a result there is much work
being done in the field to find novel prevention strategies against bacterial
infection. One area that is being looked into is the potential use of
bacteriophage viruses to kill the bacteria. The key to any drug is specificity
as this is what makes it safe and limits the side effects, so a virus which
only infects bacteria is a promising area to be looking into for ways to target
bacterial infection.
Now to move away from bacteria and back to viruses. If
bacteriophage can someday be used as an intervention against bacterial
infection, then what is to stop us going one step further and using virophage
to stop viral infection? What is to stop us from potentially producing a
virophage capable of infecting HIV or influenza or any other virus you care to
think of? Being that virophage are still a fairly new concept with only three
known of (Sputnik, Mavirus and Organic Lake virus) the prospect of producing
one capable of targeting specific viruses is some way off yet and to my
knowledge not something that is being actively looked at, the current work being
merely of the search for new virophage and understanding how they work. However
every big idea needs the ground work of discovery and understanding in order to
allow manipulation to our own ends. So perhaps in the future, instead of going
to the doctors to get a drug prescription, you may head off to the doctors to
get a virus. A crazy thought and something that may not be possible but nonetheless
fun to think about. Much of science often starts with seemingly crazy thoughts…
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