Patricia G. Spear, PhD Guy and Anne Youmans Professor and Chair Microbiology-Immunology Entry of Herpes Simplex Virus into Cells Curricula: Immunology and Microbial Pathogenesis Molecular Biology and Genetics E-mail:   p-spear@northwestern.edu

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 depends upon interactions of these glycoproteins with specific cell surface components and results from fusion of the viral envelope with a cell membrane.

We demonstrated some time ago that the initial interaction of virus with cell is binding of glycoproteins gC and/or gB to heparan sulfate chains on cell surface proteoglycans. This enables gD to bind to one of several gD receptors, which we recently identified as a previously unrecognized member of the TNF receptor family; two members of the immunoglobulin superfamily related to the poliovirus receptor; and special sites in heparan sulfate resulting from the action of specific 3-O-sulfotransferases. Interaction of gD with any one of these receptors triggers the membrane fusion reaction, which requires the concerted action of gB, gD, gH and gL as well as a gD receptor.

We have shown that mouse forms of the human gD receptors are also mediators of HSV entry. Current research is directed toward understanding the mechanism of HSV-induced membrane fusion; identifying signal transduction pathways that are activated during viral entry via different receptors; and 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.

Publications:

Yoon, M., A. Zago, D. Shukla, and P.G. Spear. (2003) Mutations in the N-termini of herpes simplex virus 1 and 2 gDs alter functional interactions with the entry/fusion receptors, HVEM, nectin-2 and 3-O-sulfated heparan sulfate, but not with nectin-1. J. Virol. 77:9221-9231.

Yoon, M., and P.G. Spear. (2002) Disruption of adherens junctions liberates nectin-1 to serve as receptor for herpes simplex virus and pseudorabies virus entry. J. Virol. 76:7203-7208.

Struyf, F., W.M. Martinez, and P.G. Spear. (2002) Mutations in the N-terminal domains of nectin-1 and nectin-2 reveal differences in requirements for entry of various alphaherpesviruses and for nectin-nectin interactions. J. Virol. 76:12940-12950.