An unusual dependence of human herpesvirus-8 glycoproteins-induced cell-to-cell fusion on heparan sulfate

Abstract

Human herpes virus 8 (HHV-8) is known to interact with cell surface heparan sulfate (HS) for entry into a target cell. Here we investigated the role of HS during HHV-8 glycoproteins induced cell fusion. Interestingly, the observed fusion demonstrated an unusual dependence on HS as evident from following lines of evidence: 1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; 2) in a competition assay, when the effector cells expressing HHV-8 glycoproteins were challenged with soluble HS, cell-to-cell fusion was reduced; and, 3) coexpression of HHV-8 glycoproteins gH-gL on target cells resulted in inhibition of cell surface HS expression. Taken together, our results indicate that cell surface HS can play an additional role during HHV-8 pathogenesis.

Prophylactic, therapeutic and neutralizing effects of zinc oxide tetrapod structures against herpes simplex virus type-2 infection

“…Since ZnOTs treatment resulted in a decreased viral entry and internalization, we decided to investigate its effect on virus free cell-to-cell fusion. To create this scenario in vitro CHO-K1 cells were split into two populations: target cells, and effector cells (Tiwari et al, 2009). Target cells were transfected with the gD receptor Nectin-1 and the luciferase reporter gene under the control of the T7 promoter.…”

A Kaposi's Sarcoma-Associated Herpesvirus Infection Mechanism Is Independent of Integrins α3β1, αVβ3, and αVβ5

“…It is thought that HS broadly acts as an attachment factor for many viruses, but some publications indicate that HS may have additional functions during KSHV infection of several cell types. One study reported that HS was required on target HEK293, Chinese hamster ovary (CHO), and human conjunctival epithelial cells in a virus-free fusion assay with effector cells that expressed KSHV gB, gH, and gL, suggesting that HS is involved in the interactions between KSHV glycoproteins and entry receptors (39). A second study used advanced imaging to reveal that upon initial binding to HT1080 fibrosarcoma cells, KSHV colocalized with HS only about half of the time, while colocalization with canonical integrin receptors was much more robust (28).…”

“…A smaller number of studies have examined select receptors on some epithelial cell lines, but such a unified model of KSHV receptor usage and mechanism of entry has not yet been assembled for any individual cell line. Soluble heparin or the enzymatic removal of HS from the cell surface inhibits KSHV infection of human embryonic kidney HEK293 cells and human conjunctival epithelial cells, suggesting that HS is required for epithelial cell infection (17,25,38,39). EphA2 is also clearly important for KSHV infection of several cell lines.…”

Inhibition of Myosin Light Chain Kinase Can be Targeted for the Development of New Therapies against Herpes Simplex Virus Type-1 Infection

“…A standard entry assay was performed as described previously [11,17]. Briefly, HCE cells were seeded at a density of 2×10 4 In addition to an ONPG assay, an entry assay was performed to quantify b-galactosidase expression by insoluble 5-bromo-4-chloro-3-indoyl-b-D-galactosidase (X-gal; Invitrogen, Grand Island, NY, USA) as described previously [17,18]. Briefly, HCE cells were grown in a 6-well plate to 100% confluence and treated with 10 mM of ML-7, ML-9 or blebbistatin, or mock-treated (DMSO) before infection with HSV-1gL86 reporter virus.…”