VIRAL AND CELLULAR-REQUIREMENTS FOR ENTRY OF HERPES-SIMPLEX VIRUS TYPE-1 INTO PRIMARY NEURONAL CELLS

Herpes simplex virus (HSV) causes many disease states including mucosa l lesions, encephalitis or disseminated infection in the immunocomprom ised host. These diverse clinical manifestations reflect the capacity of the virus to infect both epithelial and neuronal cell types. Determ ining the requirements for virus entry into both cell types may provid e insights into the pathogenesis of HSV, Previous studies have focused on identifying viral and cellular requirements for entry using epithe lial cells, However, little is known about the requirements for bindin g and entry into neuronal cells, The purpose of the studies reported h ere was to identify viral and cellular components involved in entry of HSV-1 into primary neuronal cells. Heparan sulfate glycosaminoglycans were found to serve as a receptor for entry of HSV-1 into primary neu ronal cells. Evidence to support this includes the findings that hepar in (an analogue of heparan sulfate) competitively inhibited virus bind ing and expression of immediate early virus gene products, In addition , heparitinase removed viral receptors and inhibited virus entry, In e pithelial cells, deletion of HSV-1 glycoprotein C (gC) results in viri ons that have reduced specific binding activity (virus particles bound per cell) and specific infectivity. However, in neuronal cells, it wa s found that deletion of gC resulted in no loss in specific binding ac tivity, but did result in significant impairment of virus entry as mea sured by expression of immediate early viral gene product. Taken toget her, these findings suggest cell-type differences in virus binding and entry and a different role for gC in neuronal cell infection.