An Important Role for Syndecan-1 in Herpes Simplex Virus Type-1 Induced Cell-to-Cell Fusion and Virus Spread

Abstract

Herpes simplex virus type-1 (HSV-1) is a common human pathogen that relies heavily on cell-to-cell spread for establishing a lifelong latent infection. Molecular aspects of HSV-1 entry into host cells have been well studied; however, the molecular details of the spread of the virus from cell-to-cell remain poorly understood. In the past, the role of heparan sulfate proteoglycans (HSPG) during HSV-1 infection has focused solely on the role of HS chains as an attachment receptor for the virus, while the core protein has been assumed to perform a passive role of only carrying the HS chains. Likewise, very little is known about the involvement of any specific HSPGs in HSV-1 lifecycle. Here we demonstrate that a HSPG, syndecan-1, plays an important role in HSV-1 induced membrane fusion and cell-to-cell spread. Interestingly, the functions of syndecan-1 in fusion and spread are independent of the presence of HS on the core protein. Using a mutant CHO-K1 cell line that lacks all glycosaminoglycans (GAGs) on its surface (CHO-745) we demonstrate that the core protein of syndecan-1 possesses the ability to modulate membrane fusion and viral spread. Altogether, we identify a new role for syndecan-1 in HSV-1 pathogenesis and demonstrate HS-independent functions of its core protein in viral spread.

Analysis of Virion-Incorporated Host Proteins Required for Herpes Simplex Virus Type 1 Infection through a RNA Interference Screen

“…Our results are also in the same range (i.e. less than a log difference) observed by others in recent studies analyzing the impact of cellular proteins on HSV or HIV proliferation [55], [56], [57], [58], [59], [60], [61]. Multi-log inhibitions where therefore not expected in the present study but it does naturally make it more difficult to ascribe a functional role to present host proteins.…”

An Investigative Peptide–Acyclovir Combination to Control Herpes Simplex Virus Type 1 Ocular Infection

“…Syndecan-1 has been implicated in HSV-1 entry into various cell types. 18 As shown in Figure 6, the uninfected cornea showed that syndecan-1 is expressed abundantly in the corneal epithelium, with some accentuation in the basal cells. There was also some staining of cells in the stroma.…”

A 3- O -Sulfated Heparan Sulfate Binding Peptide Preferentially Targets Herpes Simplex Virus 2-Infected Cells

“…After 4 h, cells were washed 3 times with 1ϫ PBS and once with citrate buffer (pH 3) to remove any bound virus particles. The Western blot assay was performed according to protocols described previously (21). Briefly, whole-cell lysates were denatured in NuPAGE LDS sample buffer (NP0007; Invitrogen, Carlsbad, CA) and heated to 86°C for 8 min before gel loading.…”