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To initiate infection, viruses first bind to
cellular receptors, then they undergo structural
transitions that are necessary to deliver viral
genetic material into the cell. These
events dictate virus tropism, and thus are
crucial determinants of viral pathogenesis.
We focus on understanding these entry processes
using murine coronavirus and its cellular
receptor as model ligands. Coronaviruses
are attractive agents for these entry studies
because they exhibit considerable natural strain
variation, and because each strain can take a
distinct pathway into host cells.
Entry begins when virion spike (S) proteins bind
to cellular adhesion molecules termed CEACAMs,
and this leads to an S protein-mediated fusion
of virion and cellular membranes. We
produce soluble CEACAMs as mimics of the
authentic receptor, then study how these ligands
alter S protein structure. A subset of
CEACAM-induced structural transitions are
required to initiate infection, and thus we
focus on the biochemical features of these
intermediate structures to promote understanding
of the complex S-mediated membrane fusion
process. Entry also requires specific
membrane environments, both on a virion coat and
on the host cell surface. We use a variety
of approaches to study coronavirus infection
after modifying the lipid composition in virion
and cellular membranes. In these ways we
will contribute to our general understanding of
enveloped virus.
Selected
Publication:
Pewe, L., Zhou, H.,
Netland, J., Tangudu, C., Olivares, H., Shi, L.,
Look, D., Gallagher, T., Perman, S. A
severe acute respiratory syndrome-associated
coronavirus-specific protein enhances virulence
of an attenuated murine coronavirus. J.
Virol. 2005 Sep;79(17):11335-42.
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