 n this interview for Special Topics, Dr. Stanley Perlman of the
University of Iowa discusses his highly cited work on coronaviruses.
In our analysis, Dr. Perlman ranks at #8 among scientists publishing
in this topic over the past decade, with 36 papers cited a total of
473 times. Dr. Perlman is a Professor of Pediatrics and Microbiology
at the Roy J. and Lucille A. Carver College of Medicine of the
University of Iowa.
|
 Why do you think your work is highly cited?
We study infections in the central nervous system of mice caused by
mouse hepatitis virus and the host immune response to these
infections. A consequence of the anti-viral host immune response is
destruction of the myelin sheath within the white matter of the spinal
cord. This results in demyelination with a disease pattern similar to
that observed in humans with multiple sclerosis. This model has been
useful for understanding some of the features of multiple sclerosis
that are not amenable to observation in humans. Our work has
identified several unique aspects of this immunopathological process.
We have identified variants of the virus that are able to evade
virus-specific cytotoxic T cells (CTL escape mutants). CTL escape
mutants have been identified in several human infections, including
those caused by hepatitis C virus and HIV. Our model is one of the
best animal models for studying CTL escape. Second, we have developed
model systems that allow us to delineate the precise effector
molecules involved in demyelination. Delineation of these factors is
important not only for understanding the pathogenesis of the disease
but also for future development of therapeutic agents for multiple
sclerosis and other related diseases.
Please describe the significance of your work on coronaviruses in
layman's terms.
This research is significant in understanding how coronaviruses are
able to persist after infection of humans or animals. As the host
tries to clear the infection, the result is destruction of parts of
the central nervous system. This results in symptoms similar to those
observed in patients with multiple sclerosis. Similar pathological
changes may occur in humans infected with the SARS-related coronavirus,
since widespread destruction of the lungs is apparent in some infected
people, without much evidence for the virus still being present.
How did you become involved in this research?
After completing medical school and a pediatric residency, I became
interested in understanding how viruses and the host immune response
to these viruses affect the central nervous system. Mice infected with
mouse hepatitis virus serve as an excellent model for investigating
these issues.
Has the current concern about SARS affected the course of your
research?
It has certainly made coronavirus research in general more timely.
Previously, we considered our work as relevant for understanding how
viruses persist in the central nervous system and the
immunopathological consequences of these infections. We are now partly
shifting our focus to understanding how the SARS-related coronavirus
causes disease in infected humans. There may be both direct viral
affects of the infection as well as disease caused by the host immune
response to the virus; we are interested in both aspects. Ultimately,
of course, we would like to make a contribution to removing this
virus as a threat to humans.
How important are these viruses in human disease?
Before the SARS epidemic began, these viruses were notable for
causing 15-25% of upper respiratory tract infections, and possibly for
occasionally causing small epidemics of diarrhea. They were associated
with several important diseases of livestock but not so much with
human disease .
Where do you see this research going 10 years from now?
If SARS turns out to be a persistent and important problem, I think
that much effort will be made to understand the pathogenesis of the
disease and to develop anti-viral agents and vaccines that will be
useful in preventing and treating the disease. While we will work on
the SARS-related coronavirus, I think that efforts to understand the
immunopathological diseases caused by the murine coronaviruses will
continue to occupy much of our efforts, since these models are very
useful for understanding many diseases with chronic inflammation, most
notably multiple sclerosis.
What lessons would you draw from your work to share with the next
generation of researchers?
Coronaviruses have been labeled a backwater virus and the relevance
of the study of these viruses to understanding human disease has been
questioned in the past. However, the SARS epidemic shows that it is
difficult to know with certainty which lines of investigation will be
most important in the future. Therefore, young investigators should
work in areas that they find interesting and pursue investigations
that lead to novel information, even if they do not seem immediately
relevant to understanding human disease.
Stanley Perlman, Ph.D., M.D.
University of Iowa
Iowa City, Iowa, USA
|
ESI Special Topics,
July 2003
Citing URL - http://www.esi-topics.com/coronavirus/interviews/StanleyPerlman.html
|
|
