Syncytium formation is induced in the murine neuroblastoma cell cultures which produce pathogenic type G proteins of the rabies virus

Abstract

We investigated comparatively the interactions of host cells with two types of rabies virus G protein, an avirulent type G (Gln) and a virulent type G (Arg) protein, having glutamine and arginine at position 333, respectively. For this purpose, we established four types of cell lines (referred to as G(Gln)-NA, G(Arg)-NA, G(Gln)-BHK, and G(Arg)-BHK cells, respectively) by transfecting either the G(Gln)-cDNA or G(Arg)-cDNA into two kinds of cells, murine neuroblastoma C1300 (clone NA) and nonneuronal BHK-21. Both G(Gln)-NA and G(Arg)-NA cells produced G proteins when they were treated with 5 mM sodium butyrate, but only G(Arg)-NA cells formed syncytia at the neutral pH, which was suppressed by anti-G antiserum. The sodium butyrate-treated G(Arg)-NA cells fused also with sodium butyrate-treated NA cells under coculture conditions, but neither with untreated NA cells nor with BHK-21 cells. On the other hand, both G(Gln)-BHK and G(Arg)-BHK cells constitutively produced G proteins, but no syncytium was produced at the neutral pH. G(Arg)-BHK cells, however, formed syncytia with the sodium butyrate-treated NA cells when they were cocultured. These results suggest that only G(Arg) has a potential ability to produce syncytia of NA cells regardless of cell types by which G(Arg) protein was produced and also suggest that a certain cellular factor(s) is required for the syncytium formation, the factor(s) which is lacking in BHK-21 and untreated NA cells but is produced by the sodium butyrate-treated NA cells.