Herpes simplex virus - induced interferon production and activation of natural killer cells in SM/J mice. Relation to antiviral resistance.

We have studied the susceptibility of SM/J mice to intraperitoneal (i.p.) infection with herpes simplex virus type 1 (HSV) and have searched for correlations of susceptibility with the activation of Natural Killer (NK) cells and with local induction of interferon. SM/J were exceedingly susceptible to virus infection as they could be killed by less than 10 plaque forming units (PFU). The NK cell system of these mice, as measured by the activity of spleen cells against YAC-1 lymphoma cells, was hyperreactive, which is in agreement with previous findings of others. The peritoneal exudate cells (PEC) of uninfected mice had no activity. However, 18 h after i.p. injection of HSV NK cell activity was detected in the PEC population, which was at least as high as that in C57BL/6 mice that are resistant to HSV infection. Thus it appears as if the NK cell system does not play a major role in antiviral resistance in our experimental system. In contrast, from our previous work it would rather appear that the magnitude of the early local interferon response is important for resistance. The current data obtained in SM/J mice are in accordance with this, in that these highly susceptible mice are deficient in their early interferon response. Homozygous beige mice were found to be as resistant to infection with HSV as C57BL/6 mice. While the NK cell activity in their PEC population after injection of HSV was low, the titers of locally induced interferon were as high as those in the controls.