Mechanism of Acquired Resistance to Herpes Simplex Virus Infection as Studied in Nude Mice

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Abstract
Summary The role of antibody and cell-mediated immunity in the resistance of adult mice to intracutaneous infection with herpes simplex virus type 1 (HSV-1) was studied in nu/nu and nu/+ mice. In nu/+ mice, local skin lesions began to appear at the site of inoculation on the 4th day after intracutaneous challenge with the virulent Hayashida strain of HSV-1. Zosteriform skin lesions were observed in some animals. Almost complete regression of the lesions had occurred by the 16th day p.i. In contrast, all of the nu/nu mice that developed local skin lesions died after development of severe zosteriform skin lesions. After repeated intraperitoneal inoculations with the avirulent SKa strain of HSV-1, nu/nu mice did not produce detectable amounts of neutralizing antibody and succumbed to infection, indicating no development of resistance. Passively transferred neutralizing antibody prevented nu/nu mice from developing zosteriform skin lesions by the Hayashida strain of HSV-1, as long as the minimum concentration of serum antibody was maintained and prolonged their survival time. Adoptive transfer of 1.0 × 107 immune nu/+ spleen cells to nu/nu mice provided almost complete recovery from infection with production of sporadic low levels of anti-HSV antibody. The protective action of the immune spleen cells was lost after pre-treatment with anti-θ serum and fresh guinea pig serum prior to transfer of the cells. These data indicate that T cell-mediated cellular immunity plays a major role in recovery from intracutaneous HSV infection in mice, while antibody-mediated protection due to passive administration of HSV antibody is effective only in limiting the spread of virus.