Thakkar Neel, Yadavalli Tejabhiram, Jaishankar Dinesh, Shukla Deepak
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA.
Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60612, USA.
Pathogens. 2017 Sep 18;6(3):43. doi: 10.3390/pathogens6030043.
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.
硫酸乙酰肝素（HS）在哺乳动物细胞中广泛表达。它是一种多糖，能结合生长因子、细胞因子和趋化因子，从而控制多种重要的生理功能。具有讽刺意味的是，包括病毒在内的许多人类病原体都与它相互作用以黏附宿主细胞。HS的功能可通过对细胞表面糖链的选择性修饰和/或选择性切割来调节。在哺乳动物中，乙酰肝素酶（HPSE）是唯一已知的能够通过选择性内切糖苷酶活性调节HS功能的酶，该活性在内切位点切割聚合的HS链。在稳态过程中，HPSE的表达及其内切糖苷酶活性受到严格调控；然而，在包括感染在内的应激条件下，其表达可能上调，这可能直接导致多种疾病病理的发生。在这里，我们以单纯疱疹病毒、登革热病毒、人乳头瘤病毒、呼吸道合胞病毒、腺病毒、丙型肝炎病毒和猪繁殖与呼吸综合征病毒为例，总结在理解HPSE酶在病毒感染、传播和发病机制中高度重要但仍在不断显现的作用方面的最新进展。
