Emerging Roles of Heparanase in Viral Pathogenesis

Abstract

Heparan sulfate (HS) is ubiquitously expressed on mammalian cells. It is a polysaccharide that binds growth factors, cytokines, and chemokines, and thereby controls several important physiological functions. Ironically, many human pathogens including viruses interact with it for adherence to host cells. HS functions can be regulated by selective modifications and/or selective cleavage of the sugar chains from the cell surface. In mammals, heparanase (HPSE) is the only known enzyme capable of regulating HS functions via a selective endoglycosidase activity that cleaves polymeric HS chains at internal sites. During homeostasis, HPSE expression and its endoglycosidase activity are tightly regulated; however, under stress conditions, including infection, its expression may be upregulated, which could contribute directly to the onset of several disease pathologies. Here we focus on viral infections exemplified by herpes simplex virus, dengue virus, human papillomavirus, respiratory syncytial virus, adenovirus, hepatitis C virus, and porcine respiratory and reproductive syncytial virus to summarize recent advances in understanding the highly significant, but emerging roles, of the enzyme HPSE in viral infection, spread and pathogenesis.

Non-Anticoagulant Heparins as Heparanase Inhibitors

“…The role of heparanase enzymatic activity in supporting viral infection has recently emerged, suggesting new potential applications of heparanase inhibitors [134] (Angelidis and Shukla, Chap. 32 in this volume).…”

Forty Years of Basic and Translational Heparanase Research

“…Nowadays, heparanase is well established as a cancer drug target, and several inhibitors have progressed to clinical trials [31,34]. In recent years, heparanase has also been implicated in a range of other diseases, such as diabetes and its complications [35][36][37], kidney disease [38], atherosclerosis [39,40] and viral infections [41], to name a few, which continues to fuel research into this protein.…”

Helicobacter�pylori infection enhances heparanase leading to cell proliferation via mitogen‑activated protein kinase signalling in human gastric cancer cells

“…Multiple studies have demonstrated that H. pylori infection induces gastric cancer by activating NF-κB (30,31). It has also been reported that NF-κB can increase the expression of HPA in multiple tumours (32,34,59,60). Specifically, studies have revealed that NF-κB was closely associated with the expression of HPA in gastric cancer cells and tissues (61,62).…”