Glycosaminoglycan Compositional Analysis of Relevant Tissues in Zika Virus Pathogenesis and in Vitro Evaluation of Heparin as an Antiviral against Zika Virus Infection

• DOI: 10.1021/acs.biochem.8b01267
• Publication Date: 2019-01-30T17:44:58Z
• Authors: So Young Kim; Cheri A. Koetzner; Anne F. Payne; Gregory J. Nierode; Yanlei Yu; Rufeng Wang; Evan Barr; Jonathan S. Dordick; Laura D. Kramer; Fuming Zhang; Robert J. Linhardt
• Keywords: Zika Virus; Pathogenesis; Flavivirus; Vero cell; Tissue tropism

Zika virus (ZIKV) is an enveloped RNA from the flavivirus family that can cause fetal neural abnormalities in pregnant women. Previously, we established ZIKV-EP (envelope protein) binds to human placental chondroitin sulfate (CS), suggesting CS may be a potential host cell surface receptor ZIKV pathogenesis. In this study, further characterized GAG disaccharide composition of other biological tissues (i.e., mosquitoes, brain cells, and eye tissues) pathogenesis investigate role tissue specific GAGs. Heparan (HS) was major GAG, levels HS-6-sulfo, HS 0S (unsulfated HS), 4S disaccharides were main differences Aedes aegypti albopictus mosquitoes. progenitor differentiated disaccharides. A change observed between undifferentiated cells. different regions bovine eyes, amounts hyaluronic acid or keratan varied depending on region eye. Next, examined heparin (HP) various structures their vitro antiviral activity against Dengue (DENV) infection Vero All compounds effectively inhibited DENV replication; however, they surprisingly promoted replication. HP longer chain lengths more strongly This study expands our understanding GAGs carbohydrate-based antivirals flaviviral infection.