Effect of the deletion of US2 and US3 from herpes simplex virus type 2 on immune responses in the murine vagina following intravaginal infection.

We investigated the effects of US2 and US3 deficiencies of herpes simplex virus type 2 (HSV-2) on host immunity in a murine model of genital herpes infection. Viral clearance from the vaginal mucosa was more rapid in mice infected with a US3-deficient mutant L1BR1 as compared with a wild-type 186 or YY2 (US2-deficient mutant) infection, although there was no significant difference among them in initial growth in the early stage of infection. Flow cytometric studies revealed that the number of vaginal mononuclear cells in L1BR1-infected mice was significantly greater than that in 186- or YY2-infected mice. Dendritic cells, macrophages and T cells were induced more rapidly and in greater numbers within the vaginas of L1BR1-infected mice. Moreover, the levels of IL-12 and IFN-gamma increased in L1BR1-infected mice over levels in 186-infected mice. These results indicate that a US3 deficiency alters the induction of the host immune response; therefore, the inactivation of US3 may be a promising strategy in the development of novel vaccines for genital herpes.