Recombinant herpes simplex virus type 1 expressing murine interleukin-4 isless virulent than wild-type virus in mice

The effect of interleukin-4 (IL-4) on herpes simplex virus type 1 (HSV-1) i nfection in mice was evaluated by construction of a recombinant HSV-1 expre ssing the gene for murine IL-4 in place of the latency-associated transcrip t (LAT). The mutant virus (HSV-IL-4) expressed high levels of IL-4 in cultu red cells. The replication of HSV-IL-4 in tissue culture and in trigeminal ganglia was similar to that of wild-type virus. In contrast, HSV-IL-4 appea red to replicate less well in mouse eyes and brains. Although BALB/c mice a re highly susceptible to HSV-1 infection, ocular infection with HSV-IL-4 re sulted in 100% survival. Furthermore, 57% of the mice survived coinfection with a mixture of HSV-IL-4 and a lethal dose of wild-type McKrae, compared with only 10% survival following infection with McKrae alone. Similar to wi ld-type BALB/c mice, 100% of IL-4(-/-) mice also survived HSV-IL-4 infectio n. T-cell depletion studies suggested that protection against HSV-IL-4 infe ction was mediated by a CD4(+)-T-cell response.