Intracerebral inoculation of newborn and adult mice with thymidine kinase-deficient mutants of herpes simplex virus type 1

It has been reported that TK^- mutants of HSV-1 are less pathogenic and induce lower rates of latent sensory ganglion infection than do standard TK⁺ viruses. In part, this may be due to impaired replication of TK^- HSV-1 in ganglionic neurons. Recently, TK^- HSV has been isolated from patients after treatment with acyclovir, an antiviral drug that is phosphorylated to the active form by HSV TK. However, the exact role of HSV TK expression in disease production remains to be determined. Based on several observations, we hypothesized that decreased virulence of TK^- HSV strains in vivo was due to abortive infection of nonreplicating neurons. To further test the virulence of TK^- HSV, we studied infection after intracerebral inoculation of adult and newborn mice.