Download Andrew Kilianski

Abstract
Our bodies have many complex mechanisms in place for defending against viral
infection. However, viruses have evolved ways to circumvent or disrupt these innate defenses in
order to replicate and cause disease. My project aims to understand how Severe Acute
Respiratory Syndrome Coronavirus (SARS-CoV) caused a deadly outbreak and epidemic in
2002-2003. SARS is characterized by a lack of early recognition and signaling by the immune
system, and it has since been discovered that SARS-CoV encodes many proteins that are
important in blocking our innate immune response to viruses. SARS-CoV encodes a papain-like
protease, PLpro, which is important for viral replication but also blocks components of our
innate immune system within virally infected cells. The goal of my project is to determine how
PLpro interacts with host factors during viral infection, and if blocking the interaction of PLpro
with host factors causes a reduction in virulence. If disrupting PLpro activity is detrimental to
the virus, my project opens up a great candidate protein for antiviral drug and vaccine
development.
Summer Research
My summer undergraduate will work closely with me in using targeted mutagenesis to
affect the function of SARS-CoV PLpro. Using mutagenesis, we can change the cellular activity
of PLpro to examine how PLpro interacts with the innate immune system and how this
interaction is beneficial to the virus. This includes generation of novel PLpro mutants by PCR
and testing the activity of PLpro mutants using gene reporter assays in a cell culture based
system. This work will usually require six to eight hours a day for five days a week during
normal working hours. In addition to learning how to think and work like a virologist, the
Microbiology and Immunology Department offers many seminars and presentations which are
not only interesting but cover a variety of topics which the student can also participate in.