An essay published in PLOS Pathogens' new "Research Matters" series
reflects on a career path that started with the study of a somewhat obscure
mouse virus mice and ended up at the frontline of the SARS and MERS coronavirus
epidemics.
His curiosity about basic cell biology and the desire to understand the
devastating effects of viruses on the developing human brain led Stanley
Perlman, from the University of Iowa's Carver School of Medicine, Iowa City,
USA, to dedicate the work of his research group to the study of a virus that
infects the mouse brain, murine hepatitis virus (MHV), a member of the
coronavirus family, and the mammalian immune response to it.
Their work showed that while the immune response to MHV infection is
essential to controlling the infection, it is also responsible for many of the
clinical symptoms that occur, including the destruction of a certain type of
nerve cell. Incidentally, these results from the mouse model studies stem turned
out to be highly relevant to the human multiple sclerosis.
Perlman and colleagues also showed that the immune response to MHV involves
an intricate interplay of different immune cells, and that unless it is dampened
appropriately after the initial destructive attack on the invading virus, some
of these cells will damage and even destroy the host's own tissues. A key role
in controlling the immune response, they found, was played by so-called
"regulatory T cells," a finding that is now well-established and central to many
current approaches to prevent or treat autoimmune and other inflammatory
diseases.
As Perlman states, while "until the early 2000s, coronaviruses were not
considered important human pathogens," the main reason for "rapid progress in
understanding SARS and MERS and in developing vaccines and therapies was
existing knowledge gained from studies of MHV and other animal
coronaviruses."
Besides MHV, Perlman's laboratory now also studies three human
coronaviruses and has developed a mouse model for MERS. His "journey from
studies of murine coronaviruses to those of serious human pathogens," he says,
illustrates the importance of research driven initially by curiosity." "It is
only through basic research into these pathogens," he concludes, "that we will
be prepared for future outbreaks."
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