Determination of heterogeneity of glycoprotein and tegument proteins in HSV1, and the functional significance of the HSV1 gH-integrin interaction. (360G-Wellcome-082108_Z_07_Z)

Determining the extent to which populations of complex enveloped viruses exhibit compositional heterogeneity is of fundamental importance for understanding aspects of virus entry, morphogenesis and pathogenesis. We will determine the variation in terms of glycoprotein and tegument composition in populations of Herpes Simplex virus Type 1 (HSV1) at the single particle level using highly-sensitive fluorescence-based confocal spectroscopy. We will subsequently compare heterogeneity profiles of vi rus populations propagated under conditions that are biologically relevant to HSV1 infection, and will determine the influence of tegument and glycoprotein deletions on virion-to- virion compositional make-up. We will also determine the functional and biological significance of the interaction between HSV1 glycoprotein H (gH) with host cell integrin molecules. We have found that purified recombinant gH protein binds to cells expressing alpha-v-beta-3 integrins, and now wish to ascertain the rel evance of this interaction, both in terms of the entry of HSV1 into specific cell types, and the ability of HSV1 to induce intracellular signalling pathways.