Delayed IgG-mediated clearance of herpes simplex virus type 1 from the CNS but not footpad during the early stages of infection: possible result of relative integrity of the blood-brain barrier.

Following footpad inoculation in mice, herpes simplex virus type 1 spreads along nerves to the spinal cord where a myelitis causes hind limb paralysis beginning on day 6. Neutralizing antibody effectively prevents this illness only if given within 72 h. We therefore studied the timing of blood-brain barrier (BBB) disruption relative to the appearance of virus and inflammatory cell infiltrates in the spinal cord. Virus was detectable in dorsal root ganglion and spinal cord explants by 48 h. By 72 h, mononuclear cell infiltrates were evident in the spinal cord. By day 4, high titres of virus were demonstrable in the spinal cord. On day 6 125I-labelled IgG tracers penetrated the spinal cord BBB. In addition, using a passive transfer model, mice given neutralizing IgG completely cleared footpad virus within 72 h while brain virus titres were unaffected by IgG treatment up to day 7. These observations indicate that the BBB may prevent IgG-mediated virus clearance during the early stages of infection.