Archaic connectivity between the sulfated heparan sulfate and the herpesviruses – An evolutionary potential for cross-species interactions

James Elste, Angelica Chan, Chandrashekhar Patil, Vinisha Tripathi, Daniel M. Shadrack, Dinesh Jaishankar, Andrew Hawkey, Michelle Swanson Mungerson, Deepak Shukla, Vaibhav Tiwari*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

The structural diversity of metazoic heparan sulfate (HS) composed of unique sulfated domains is remarkably preserved among various vertebrates and invertebrate species. Interestingly the sulfated moieties of HS have been known as the key determinants generating extraordinary ligand binding sites in the HS chain to regulate multiple biological functions and homeostasis. One such ligand for 3-O sulfation in the HS chain is a glycoprotein D (gD) from an ancient herpesvirus, herpes simplex virus (HSV). This interaction between gD and 3-O sulfated HS leads to virus-cell fusion to promote HSV entry. It is quite astonishing that HSV-1, which infects two-thirds of the world population, is also capable of causing severe diseases in primates and non-primates including primitive zebrafish. Supporting evidence that HSV may cross the species barrier comes from the fact that an enzymatic modification in HS encoded by 3-O sulfotransferase-3 (3-OST-3) from a vertebrate zoonotic species enhances HSV-1 infectivity. The latter phenomenon suggests the possible role of sulfated-HS as an entry receptor during reverse zoonosis, especially during an event when humans encounter domesticated animals in proximity. In this mini-review, we explore the possibility that structural diversity in HS may have played a substantial role in species-specific adaptability for herpesviruses in general including their potential role in promoting cross-species transmission.

Original languageEnglish (US)
Pages (from-to)1030-1040
Number of pages11
JournalComputational and Structural Biotechnology Journal
Volume21
DOIs
StatePublished - Jan 2023

Funding

This work was supported by Midwestern University One Health Research Stimulus Award. to VT and MSM.

Keywords

  • Heparan sulfare
  • Sulphated heparan sulfate
  • Virus cell fusion
  • Virus cell-to-cell spread
  • Virus entry

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Computer Science Applications

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