Interleukin-12- and gamma interferon-dependent innate immunity are essential and sufficient for long-term survival of passively immunized mice infected with herpes simplex virus type 1

Interferon (IFN) type I (alpha/beta IFN [IFN-alpha/beta]) is very important in directly controlling herpes simplex virus type I (HSV-1) replication as well as in guiding and upregulating specific immunity against this virus. By contrast, the roles of IFN type II (IFN-gamma) and antibodies in the def ense against HSV-1 are not clear. Mice without a functional IFN system and no mature B and T cells (AGR mice) did not survive HSV-1 infection in the p resence or absence of neutralizing antibodies to the virus. Mice without a functional IFN type I system and with no mature B and T cells (AR129 mice) were unable to control infection with as little as 10 PFU of HSV-1 strain F . By contrast, in the presence of passively administered neutralizing murin e antibodies to HSV-1, some AR129 mice survived infection with up to 10(4) PFU of HSV-1. This acute immune response was dependent on the presence of i nterleukin-12 (IL-12) p75. Interestingly, some virus-infected mice stayed h ealthy for several months, at which time antibody to HSV-1 was no longer de tectable. Treatment of these virus-exposed mice with dexamethasone led to d eath in approximately 40% of the mice. HSV-1 was found in brains of mice th at did not survive dexamethasone treatment, whereas HSV-1 was absent in tho se that survived the treatment. We conclude that in the presence of passive ly administered HSV-1-specific antibodies, the IL-12-induced IFN-gamma -dep endent innate immune response is able to control low doses of virus infecti on. Surprisingly, in a significant proportion of these mice, HSV-1 appears to persist in the absence of antibodies and specific immunity.