Erin Mckinley's Research
From the common cold
to HIV, we are all too familiar with the symptomatic effects of
a viral infection. But in order to treat or prevent
such infections, we have to learn more about the virus in general-its
structure, replication mechanism, etc. Scientists have come a long
way, but because so many different types of viruses exist, each
with their own unique characteristics, we still have a long way
to go. The virus we are working with is called reovirus. All of
us have antibodies to protect ourselves against reovirus infection-that
means that reovirus doesn't cause us to be sick or have some other
negative reaction.So, you might wonder why we are even studying
this virus if it poses us no threat.
The answer is, that by learning
more the reovirus we can learn more about viral pathogenesis in
general. The information we learn from this model system could possibly
be applied to vaccines (which are attenuated viruses) or other viruses
that are harmful. The
reovirus can be thought of as a little package of RNA wrapped in
two concentric layers of protein. I've even compared it to a peanut
M&M-you've got the important genetic code in the middle (the
peanut) protected by an outer shell of protein (the chocolate).
When the reovirus infects a cell, the outer shell breaks apart and
falls of, allowing the virus to start replicating and taking over
its host. The interactions between surface proteins in this outer
shell determines the stability of the virus in environments between
hosts. The stronger these interactions, the more resistant viruses
may be to the many different chemical and physical agents that threaten
|An electron micrograph
image of an animal reovirus. This image was used with permission from
Queen's Univeristy at was obtained from www.virology.net.
On the other hand, if these
proteins bind to eachother too strongly and can't be removed from
the outer shell (i.e. you can't bite through the chocolate to get
to the peanut) then the virus won't be able to replicate. Thus,
reoviruses face a trade-off between the stability of the outer shell
necessary for survival between host cells and the "instability"
of the outer shell essential for uncoating and replication within
the host cell. A balance must be struck between the two opposing
requirements (i.e. extracellular stability vs. intracellular "instability")
representing a fundamental dilemma that must be solved by the virus.
My experiment involves seven
reovirus mutants that were isolated by my professor (Dr. David R.
Wessner) as a grad student at Harvard. These mutants show an increased
resistance to ethanol (an agent commonly used to disinfect). Our
goal has been to determine whether these mutants are only ethanol
resistant or are generally more stable, i.e. general stability mutants.
To achieve this determination we have exposed the mutants to elevated
temperature (which normally denature a protein and thus "kill"
the virus) and phenol to see if they also show an increased resistance
to these inactivating agents. The data from these experiments, in
conjunction with past research, will help us better understand some
of the interactions among proteins in the outer shell.