Resistance of C3H/HeJ Mice to Lethal Challenge with Herpes Simplex Virus

In vitro replication of herpes simplex virus (HSV) in murine spleen cells requires simultaneous cell stimulation with a B-cell mitogen such as lipopolysaccharide (LPS). As expected, spleen cells of LPS-unresponsive C3H/HeJ mice did not support HSV replication in LPS-pretreated cultures, while spleen cells from closely related but LPS-responsive C3HeB/FeJ did. More importantly, the C3H/HeJ strain was found to be intrinsically resistant to HSV infection in vivo. After intraperitoneal (ip) inoculation, HSV was 50-120 times more virulent for C3HeB/FeJ mice than for the C3H/HeJ strain. This resistance appeared to be due to a failure of HSV to replicate in C3H/HeJ peritoneal cells, since after ip infection with HSV, recovery of virus was higher and more consistent from peritoneal exudate cells of C3HeB/FeJ mice than from C3H/HeJ mice. In addition, no difference in lethality was observed between these two strains after a direct intracerebral inoculation of HSV. This observation that LPS-unresponsive mice are intrinsically resistant to lethal HSV infection, coupled with the LPS requirement for HSV replication in vitro, suggests an important but as yet unexplained link between host sensitivity to HSV and to LPS.