HSV-1 interaction to 3-O-sulfated heparan sulfate in mouse-derived DRG explant and profiles of inflammatory markers during virus infection.
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.
Department of Anatomy, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, 60515, USA.
Harsh
H
Sharthiya
Department of Biomedical sciences, College of Health Sciences, Midwestern University, Downers Grove, IL, 60515, USA.
Chanmoly
C
Seng
Department of Biochemistry, Nijmegen Institute for Molecular Life Sciences, Radboud University, 6500 HB, Nijmegen, The Netherlands.
T H
TH
Van Kuppevelt
Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, 60515, USA. vtiwar@midwestern.edu.
Vaibhav
V
Tiwari
Department of Anatomy, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, 60515, USA. mforna@midwestern.edu.
Michele
0000-0003-1852-9167
M
Fornaro
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D054365:Chemokine CXCL5 / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D015870:Gene Expression; D005966:Glucuronidase / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006868:Hydrolysis; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D061251:Primary Cell Culture; D059010:Single-Cell Analysis / Q000379:methods; D046509:Tissue Culture Techniques; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects; D000099175:Heparanase
D015415:Biomarkers; D054365:Chemokine CXCL5; D005966:Glucuronidase; D006497:Heparan Sulfate; D016173:Macrophage Colony-Stimulating Factor; D019716:Tissue Inhibitor of Metalloproteinase-2; D014759:Viral Envelope Proteins; D000099175:Heparanase; C094739:Cxcl5 protein, mouse; C562160:glycoprotein B, human herpesvirus 1; C039447:glycoprotein D, Human herpesvirus 1
HSV entry; Heparan sulfate; Neuroinflammation; Sensory neurons