Patricia
Spear, PhD
Guy and Anne Youmans Professor
Department of Microbiology/Microimmunology
To contact Dr. Spear:
Phone: 312-503-8230
E-mail: p-spear@northwestern.edu
Dr. Spear's website
PubMed
Reference Lookup
Research Interests
Herpes simplex virus (HSV) causes various forms of disease from lesions on
the lips, eyes or genitalia to encephalitis or disseminated disease. The virus
encodes about 100 proteins from a DNA genome, which is packaged within an
icosahedral shell and a lipid-protein envelope. Five of the dozen envelope
glycoproteins have been shown to have a role in viral entry into cells. Entry
results from interactions of these glycoproteins with specific cell surface
components, leading to fusion of the viral envelope with the cell membrane.
The laboratory of Dr. Patricia Spear demonstrated some time ago that the initial
interaction of virus with cell is through binding of glycoproteins gC and/or
gB with heparan sulfate chains on cell surface proteoglycans. This enables
gD to bind to one of several gD receptors, which they recently identified
as HveA, a previously unrecognized member of the TNF receptor family; HveC,
a member of the immunoglobulin superfamily related to the poliovirus receptor;
or special sites on heparan sulfate resulting from the action of specific
3-O-sulfotransferases. Interaction of gD with one of these receptors triggers
the membrane fusion reaction, which requires the concerted action of gB, gD,
gH and gL.
The latest results from Dr. Spear’s lab show that the mouse forms of
the human gD receptors are also mediators of HSV entry. Future work will be
directed toward understanding the mechanism of viral entry via different gD
receptors and toward defining the cell determinants of infection in the various
differentiated cell types that are targeted by HSV, including epithelial cells
and neurons, and in mouse models of disease.