Glycoprotein gI of pseudorabies virus promotes cell fusion and virus spread via direct cell-to-cell transmission.

Mutants of pseudorabies virus defective in either glycoprotein gI or gIII are only slightly less virulent for mice and chickens than is wild-type virus, while mutants defective in both gI and gIII are avirulent. To clarify the reason for the lack of virulence of the gI- gIII- mutants, we have analyzed in some detail the interactions of these mutants with their hosts. The results obtained showed that the gI glycoprotein is an accessory protein that promotes cell fusion. This conclusion is based on the findings that in some cell types, syncytium formation is significantly reduced in mutants deficient in gI. Furthermore, despite efficient replication, gI- mutants form significantly smaller plaques on some cell types. Finally, while wild-type and gI- virus are neutralized similarly by antisera, the size of the plaques formed by gI- mutants, but not by wild-type virus, is reduced by the presence of neutralizing antibodies in the overlay. Passive immunization of mice with neutralizing antipseudorabies virus sera is also considerably more effective in protecting them against challenge with gI- mutants than in protecting them against challenge with wild-type virus. These results show that gI- mutants are deficient in their ability to form syncytia and to spread directly by cell-to-cell transmission and that these mutants spread mainly by adsorption of released virus to uninfected cells. Wild-type virus and gIII- mutants, however, spread mainly via direct cell-to-cell transmission both in vivo and in vitro. We postulate that the lack of virulence of the gIII- gI- virus is attributable to its inability to spread by either mode, the defect in gIII affecting virus spread by adsorption of released virus and the defect in gI affecting cell-to-cell spread. Although a gI- gIII- mutant replicates as well as a gIII- mutant, it will be amplified much less well. Our results with in vitro systems show that this is indeed the case.