Heparanase, Heparan Sulfate and Viral Infection

The story of heparanase (HPSE) in viral infection has roots in the longstanding connection between heparan sulfate (HS) and a large number of viruses. As a major viral attachment and entry receptor present on the cell surface, HS serves as the first point of contact between a virus particle and its target host cell. Likewise, direct regulation of HS levels on the cell surface by HPSE enzymatic activity dictates the extent of virus release after replication has occurred. Additionally, virus-induced HPSE activation and nuclear translocation results in higher expression of pro-inflammatory factors and delayed wound healing leading to worsened disease. In this chapter, using herpes simplex virus (HSV) as a prototype virus we provide a brief synopsis of important stages in viral infection, describe how these processes are governed by HS and HPSE, and discuss the recent discoveries that designate HPSE as a major host virulence factor and driver of pathogenesis for several different viruses.