Herpes simplex virus type 1 shows multiple interactions with sulfonated compounds at binding, penetration, and cell-to-cell passage

Virus Genes (2007) 34:241248 DOI 10.1007/s11262-006-0016-5

Herpes simplex virus type 1 shows multiple interactions with sulfonated compounds at binding, penetration, and cell-to-cell passage

Jos Santiago Aguilar Katherine S. Held Edward K. Wagner

Received: 10 March 2006 / Accepted: 3 May 2006 / Published online: 22 August 2006 Springer Science+Business Media, LLC 2006

Abstract Herpes simplex virus type 1 (HSV-1) uses multicomponent mechanisms for binding, penetration, and cell-to-cell passage. These processes are affected by polysulfonated compounds. In this paper we have addressed the question of whether the same or different interactions of HSV-1 with polysulfonated compounds are involved in binding, penetration, and passage. For this, we have compared the inhibitory doseresponse for a series of polysulfonated and cationic compounds known to block HSV-1 infections. These comparisons were done at the level of binding, penetration, and cell-to-cell passage. Variations in the parameters of the doseresponse curvesIC50 and Hill

coefcients (nH)are consistent with HSV-1 having multiple interactions with sulfonated cellular components in all these processes. Some of the interactions seem to be common to the three processes, while others are particular for each one.

Keywords HSV-1 Infection Polysulfonates Binding Penetration Passage

Introduction

Herpes simplex virus type 1 (HSV-1) may utilize multiple-component mechanisms for binding, penetration, and cell-to-cell passage involving different glycoproteins [1]. The initial attachment of HSV-1 to the cell is mediated by glycoprotein C (gC) interacting mainly with heparan sulfatea glycosaminoglycan (GAG) on the cell membrane; however, when gC is absent, gB can bind properly to the cells in vitro [24]. After binding, there is a fusion of the viral envelope with the cell membrane. This fusion is mediated by gB, gD, gK, and the complex gHgL [3, 59]. Glycoprotein D exerts its action by interacting specically with several cellular proteins that can serve as receptors for HSV-1 and other related viruses; the cellular proteins most frequently used as receptors belong to the nectin family [see 1013 for reviews]. Cell-to-cell passage seems to be a process with overlapping but different mechanisms from virus entry, because it requires the same set of glycoproteins involved in virus entry plus the complex gEgI that localizes at the cellcell junctions facilitating virus transmission at these sites [1416]. In addition, gG, gM, and UL45 participate in cell-to-cell passage of syncytial strains, but...