Possible neural basis for age-dependent resistance to neurologic disease from herpes simplex virus.

Twenty-week-old mice are known to be resistant to HSV induced neurologic disease, while 5-week-old mice are susceptible. Although age-dependent resistance to disease has been attributed to immunologic maturation, most immunologic development is complete by about 3 weeks of age. We, therefore, postulated that differences in neural spread were involved and we compared the pathogenesis of viral spread in 5-week- and 20-week-old mice. Following footpad infection with 10(5.3) PFU HSV-1, virus was detected in homogenates of sciatic nerve and spinal cord 3-4 days sooner in 5-week-old versus 20-week-old mice. Virus titers in footpad homogenates were 10(5.2) to 10(6.0) in both groups, thus differences in virus replication or immunologic restriction at the initial site of infection could not account for the difference in neural spread. The rate of virus spread to the dorsal root ganglia (DRG) was assessed by ganglia explant/co-cultivation to detect virus presence at various times after footpad infection and by measuring sciatic nerve length. In 5- and 20-week-old mice the rate of virus spread to DRG was 28 mm/day and 4-12 mm/day respectively. We conclude that neural uptake and/or transport of virus may contribute to the difference in susceptibility to neurologic disease.