Characterization of cell-cell fusion mediated by herpes simplex virus 2 glycoproteins gB, gD, gH and gL in transfected cells

The mechanisms by which herpes simplex viruses (HSV) mediate fusion between their envelope and the plasma membrane during entry into cells, and betwee n the plasma membranes of adjacent infected and uninfected cells to form mu ltinucleated giant cells, are poorly understood, Four viral glycoproteins ( gB, gD, gH and gL) are required for virus-cell fusion, whereas these plus s everal others are required for cell-cell fusion (syncytium formation). A be tter understanding would be aided by the availability of a model system, wh ereby fusion could be induced with a minimal set of proteins, in the absenc e of infection. A suitable system has now been developed for HSV-2, using t ransfected COS7, 293 or HEp-2 cells, Insofar as the minimal set of HSV-2 pr oteins required to cause cell-cell fusion in this system is gB, gD, gH and gL, it would appear to resemble virus-cell fusion rather than syncytium for mation. However, the ability of a mutation in gB to enhance the fusion of b oth transfected cells and infected cells, while having no effect on virus-c ell fusion, points to the opposite conclusion. The differential effects of a panel of anti-HSV antibodies, and of the fusion-inhibitor cyclosporin A, confirm that the fusion of transfected cells shares some properties with vi rus-cell fusion and others with syncytium formation. It may therefore prove useful for determining how these processes differ, and for testing the hyp othesis that some viral proteins prevent membrane fusion until the appropri ate point in the virus life-cycle, with other proteins then overcoming this block.