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.

Highlights

  • Heparan sulfate (HS) is a glycosaminoglycan primarily made of repeating disaccharide units of glucosamine and glucuronic acid [1,2]

  • Expression levels of HPSE messenger ribonucleic acid (mRNA) positively correlated with marked proteinuria and urinary protein level, at 24 h post infection; this could be important to the loss of negative charged moieties in the glomerular basement membrane, aiding to the pathogenesis of Respiratory Syncytial Virus (RSV)

  • Heparanase was already implicated in inflammation, angiogenesis, and cancer progression and over the past few years significant new progress has been made in elucidating some unique functions of HPSE in viral infection and dissemination

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Summary

Introduction

Heparan sulfate (HS) is a glycosaminoglycan primarily made of repeating disaccharide units of glucosamine and glucuronic acid [1,2]. Unique sulfation of glucosamine especially at 2-O, 3-O, and 6-O positions adds structural diversity, which is further enhanced by site specific epimerization of the glucuronic acid residues [1,4,5] These modifications provide structural integrity and enable HS to take part in affinity-driven cellular processes including direct interactions with various growth factors, chemokines, and cytokines [2]. Since the area of research that focuses on mammalian HPSE and viral infections is still emerging only a few papers were found It was very clear from the existing literature that HPSE plays an integral role in regulating the lifecycle of many pathogenic human viruses including HSV, dengue virus, human papillomavirus, hepatitis B virus, and hepatitis C virus (Table 1). This review will, outline the versatile roles of HPSE in virus-host interactions and comment on the future potential of HPSE in effective control of human viral diseases

Schematics
Dengue
Schematic
Schematics of HPSE’s role inrole
Future Therapeutic Potential of Targeting HPSE in Viral Diseases
Findings
10. Future Prospects and Conclusions

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