GLYCOPROTEIN-E AND GLYCOPROTEIN-I FACILITATE NEURON-TO-NEURON SPREAD OF HERPES-SIMPLEX VIRUS

Two herpes simplex virus (HSV) glycoproteins E and I (gE and gI) form a heterooligomer which acts as an Fc receptor and also facilitates cel l-to-cell spread of virus in epithelial tissues and between certain cu ltured cells. By contrast, gE-gI is not required for infection of cell s by extracellular virus. HSV glycoproteins go acid gJ are encoded by neighboring genes, and go is required for both virus entry into cells and cell-to-cell spread, whereas gJ has not been shown to influence th ese processes. Since HSV infects neurons and apparently spreads across synaptic junctions, it was of interest to determine whether go, gE, g I, and gJ are also important for interneuronal transfer of virus. We t ested the roles of these glycoproteins in neuron-to-neuron transmissio n of HSV type 1 (HSV-1) by injecting mutant viruses unable to express these glycoproteins into the vitreous body of the rat eye. The spread of virus infection was measured in neuron-rich layers of the retina an d in the major retinorecipient areas of the brain. Wild-type HSV-1 and a gJ(-) mutant spread rapidly between synaptically linked retinal neu rons and efficiently infected major retinorecipient areas of the brain . go mutants, derived from complementing cells, infected only a few ne urons and did not spread in the retina or brain. Mutants unable to exp ress gE or gI were markedly restricted in their ability to spread with in the retina, produced 10-fold-less virus in the retina, and spread i nefficiently to the brain. Furthermore, when compared with wild-type H SV-1, gE(-) and gI(-) mutants spread inefficiently from cell to cell i n cultures of neurons derived from rat trigeminal ganglia. Together, o ur results suggest that the gE-gI heterooligomer is required for effic ient neuron-to-neuron transmission through synaptically linked neurona l pathways.