Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Spear, Patricia G.
Location Northwestern University
Primary Field Microbial Biology
Secondary Field Immunology and Inflammation
 Election Citation
Spear is a microbiologist whose seminal research has unraveled the complex mechanisms that allow herpes simplex viruses to enter cells. She has identified the structures on both the cells and the virus that attach the virus to the cell membrane, as well as the additional proteins needed for these to enter cells.
 Research Interests
I am interested in the mechanisms by which viruses invade cells, partricularly herpes simplex virus. Five of the viral envelope glycoproteins participate in viral entry into cells. We showed that the initial interaction of virus with cell is usually the binding of viral glycoproteins gB or gC to heparan sulfate chains on cell surface proteoglycans. In the years since, many other viruses and other microbes have been found to bind to heparan sulfate, a ubiquitous cell surface carbohydrate. Attachment of herpes simplex virus to heparan sulfate is not sufficient for entry. Entry requires the binding of a specific viral glycoprotein, gD, to any one of several different cell surface receptors, which we identified by expression cloning. The expression and distribution of these various gD receptors determine susceptibility of the cell to viral entry. Viral entry occurs by fusion of the viral envelope with the cell membrane. This fusion is triggered by the binding of gD to a gD receptor and requires the action of three other viral glycoproteins. Structure-function studies of the viral glycoproteins, entry receptors, and other cellular components will lead to an understanding of the mechanism of viral entry.

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