The Role of Interferon in the Resistance of CS7BL/6 Mice to Various Doses of Herpes Simplex Virus Type 1

C57BL/6 (B6) mice are relatively resistant to infection with herpes simplex virus type 1 (HSV-1). Paradoxically, B6 mice were resistant to 250 LD50 (50% lethal dose) of HSV-1 but were killed by 25 or 2.5 LD50 of HSV-1 injected intraperitoneally. At the injection site 250 LD50 of virus induced high titers of interferon (IFN) (greater than 1,000 international units) that reached maximal levels 2-4 hr after inoculation, whereas 25 or 2.5 LD50 of HSV-1 generated only borderline levels of IFN (15-40 international units). Simultaneous inoculation of 250 LD50 of HSV-1 and antiserum to mouse IFN (MuIFN) rendered B6 mice susceptible to infection; however, treatment with antiserum to MuIFN did not increase susceptibility to 1 LD50 of virus. Injections of MuIFN given 2 hr before and 2 hr after inoculation with virus protected B6 mice against 25 LD50 of virus. Thus, endogenous IFN induced after injection with 250 LD50 of HSV-1 protects B6 mice, whereas low doses of virus kill the animals because they do not generate a detectable IFN response at the infection site.