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

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Abstract
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. The timing of blood-brain barrier (BBB) disruption relative to the appearance of virus and inflammatory cell infiltrates in the spinal cord was studied. 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 titers of virus were demonstrable in the spinal cord. On day 6 125I-labeled IgG tracers penetrated the spinal cord BBB. Using a passive transfer model, mice given neutralizing IgG completely cleared footpad virus within 72 h while brain virus titers were unaffected by IgG treatment up to day 7. These observations indicate that the BBB may prevent IgGF-mediated virus clearance during the early stages of infection.