Heparanase (HPSE) is a multifunctional protein endowed with many non-enzymatic functions and a unique enzymatic activity as an endo-β-d-glucuronidase. The latter allows it to serve as a key modulator of extracellular matrix (ECM) via a well-regulated cleavage of heparan sulfate side chains of proteoglycans at cell surfaces. The cleavage and associated changes at the ECM cause release of multiple signaling molecules with important cellular and pathological functions. New and emerging data suggest that both enzymatic as well as non-enzymatic functions of HPSE are important for health and illnesses including viral infections and virally induced cancers. This review summarizes recent findings on the roles of HPSE in activation, inhibition, or bioavailability of key signaling molecules such as AKT, VEGF, MAPK–ERK, and EGFR, which are known regulators of common viral infections in immune and non-immune cell types. Altogether, our review provides a unique overview of HPSE in cell-survival signaling pathways and how they relate to viral infections.

乙酰肝素酶（HPSE）是一种多功能蛋白质，具有许多非酶功能和作为内切β- d-葡萄糖醛酸酶的独特酶活性。后者使其能够通过细胞表面蛋白多糖硫酸乙酰肝素侧链的良好调节裂解，充当细胞外基质 (ECM) 的关键调节剂。 ECM 的裂解和相关变化导致多种具有重要细胞和病理功能的信号分子的释放。新出现的数据表明，HPSE 的酶功能和非酶功能对于健康和疾病（包括病毒感染和病毒诱发的癌症）都很重要。本综述总结了 HPSE 在关键信号分子（如 AKT、VEGF、MAPK-ERK 和 EGFR）的激活、抑制或生物利用度中的作用的最新发现，这些信号分子是免疫和非免疫细胞类型中常见病毒感染的已知调节因子。总而言之，我们的综述提供了细胞生存信号通路中 HPSE 及其与病毒感染的关系的独特概述。