Fibroblast Growth Factor Receptor: Does It Have a Role in the Binding of Herpes Simplex Virus?

Abstract

We found that purified radiolabeled HSV could bind as well or better to the FGF receptor-deficient A-1 cells as they could to the FGF receptor-positive 4-1 cells (Fig. 1). At every concentration, about twice as much virus bound per cell to the A-1 cells as to the 4-1 cells, in the absence of heparin. The binding was inhibited by heparin, as has been shown previously for the binding of HSV to permissive HEp-2 cells (6). Because the adsorption of HSV to cells requires the presence of cell surface heparan sulfate (6), these results suggest that the faster growing 4-1 cells may express less cell surface heparan sulfate than do the control A-i cells. At the highest dose of virus tested in Fig. 1, which was not sufficient to saturate receptors for HSV, the amount ofvirus bound to the A-1 cells was about 1,800 plaque-forming units (PFU) per cell or 36,000 particles per cell. We estimate that the amount of virus required to saturate HSV receptors on permissive HEp-2 cells is 60,000 particles per cell (7). Therefore, the ability of the FGF receptor-deficient CHO cells to bind HSV may be similar to that of permissive HEp-2 cells.We also quantitated the adsorption of radiolabeled HSV to both cell lines at 370Cand determined the susceptibility of the cells to abortive infection by monitoring expression of the immediate-early HSV protein designated iCP4. Adsorption of virus was similar for the A-i and the 4-1 cells, and the two cell lines were indistinguishable with respect to the fraction of cells that expressed ICP4 (Fig. 2)

Cell surface receptors for herpes simplex virus are heparan sulfate proteoglycans.

“…It should be noted that CHO cells are markedly deficient in high affinity receptors for FGF (38,68) and yet are susceptible to HSV infection . Enhancement of FGF receptor expression by transfection of the appropriate gene into CHO cells does not enhance susceptibility of the cells to infection by HSV1(F) or HSV1(KOS) (55) . Thus, deficiency of FGF receptors does not account for the partial restriction of HSV infection observed for these HSV strains in control CHO cells.…”

Putative dengue virus receptors from mosquito cells

“…However, in view of the tissue tropism of these viruses, virus entry cannot be controlled by these ubiquitous receptor molecules alone. The role of the fibroblast growth factor receptor as a more specific receptor for herpes simplex virus type I is an example where heparan sulfate also serves as an accessory molecule [7].…”

Fibroblast growth factor 2, heparin and suramin reduce epithelial ulcer development in experimental HSV-1 keratitis

“…inhibition of lymphocyte proliferative responses to IL-1 and IL-2, inhibition of cytokine production, decreasing the interferon-enhanced expression of class II histocompatibility antigens, inhibition of cytokine-induced expression of the alternative complement pathway activator B) [8] could be responsible for a decrease in the inflammatory response. Kaner et al [21] proposed a specific interaction of HSV with the FGF receptor and concluded that this receptor may serve as a "portal" of cellular entry for the virion, an observation which was not confirmed by Shieh and Spear [27] when repeating the experiments. However, because of the recent demonstration by Yayon et al [33] that binding of FGF to heparan sulfate is obligatory for its interaction with the high-affinity receptor, we asked whether complete inhibition of viral access to both heparan sulfate and and the FGF high-affinity receptor would exert additional beneficial effects during the course of the in vivo infection.…”

“…A model of FGF-2 action in this case would be direct competition of the growth factor with the virion for binding sites on heparan sulfate proteoglycans, a prerequisite for HSV-1 adsorption and infectivity as demonstrated byWuDunn and Spear [32]. This interpretation was recently proposed by Shieh and Spear [27] to explain the inhibition of viral adsorption by FGF-2 in some cell lines in vitro. To evaluate this hypothesis further, we applied high doses of heparin to HSV-1 infected corneas.…”