The molecular mechanism of herpes simplex virus (HSV) entry and the associated inflammatory response in the nervous system remain poorly understood. Using mouse-derived ex vivo dorsal root ganglia (DRG) explant model and single cell neurons (SCNs), in this study, we provided a visual evidence for the expression of heparan sulfate (HS) and 3-O-sulfated heparan sulfate (3-OS HS) followed by their interactions with HSV-1 glycoprotein B (gB) and glycoprotein D (gD) during cell entry. Upon heparanase treatment of DRG-derived SCN, a significant inhibition of HSV-1 entry was observed suggesting the involvement of HS role during viral entry. Finally, a cytokine array profile generated during HSV-1 infection in DRG explant indicated an enhanced expression of chemokines (LIX, TIMP-2, and M-CSF)—known regulators of HS. Taken together, these results highlight the significance of HS during HSV-1 entry in DRG explant. Further investigation is needed to understand which isoforms of 3-O-sulfotransferase (3-OST)-generated HS contributed during HSV-1 infection and associated cell damage.Electronic supplementary materialThe online version of this article (doi:10.1007/s13365-017-0521-4) contains supplementary material, which is available to authorized users.

Cytomegalovirus infection cause of severe developmental disorders of the CNS. Aim: In this study, we utilized a differentiated mouse-derived hippocampal cell line (dHT22) to understand mouse CMV (MCMV) infection. Results: The expression of immediate early genes ( IE) 1 and 3 confirmed the time-dependent susceptibility of dHT22 cells to MCMV infection. MCMV infection alters the cellular distribution of heparan sulfate (HS). In addition, pretreatment with heparinase significantly reduces virus infectivity. Conclusion: The compartmentalization of HS in MCMV infected cells suggests multiple roles of HS in virus life cycle ranging from viral entry to viral transport and cellular remodeling. An enzymatic heparinase assay confirmed that HS is critical for viral entry and trafficking.