Effect of Antithymocyte Serum on Herpesvirus Hominis (type 1) Infection in Adult Mice 1

Abstract

Rabbit antimouse thymocyte (RAMT) serum, a potent suppressant of cell-mediated immunity (1), has been shown to affect the course of several viral infections in mice (2). The effect of RAMT serum on herpesvirus hominis (HVH) infection was considered of particular interest since certain clinical conditions associated with defects in the thymus-dependent cellular immune system, such as the Wiskott-Aldrich syndrome (3) may develop severe, even fatal, HVH infections. It was also desirable to ascertain if the effect of RAMT serum would depend on the route of HVH inoculation, since this was an important factor in the case of primary vaccinia infection in mice (4).

Materials and Methods. Virus strain. Earlier studies in adult mice demonstrated that neurovirulence of HVH strains depended on their antigenic type; HVH type 2 is more virulent than HVH type 1 whether inoculated intragenitally, intramuscularly, or intracerebrally (5, 6). Since all 28 HVH strains isolated from the brain or spinal fluid of patients, other than newborns, with herpetic meningoencephalitis and an isolate from a child with the Wiskott-Aldrich syndrome belonged to HVH type 1 (7), it was decided to study first the effect of RAMT serum on HVH type 1 infection in adult mice. The HVH type 1 virus used was the VR₃-Lennette strain, recovered from the brain of a patient with herpetic encephalitis (7). Its titer, as assayed in primary rabbit kidney tissue culture, was 10⁷ TCID₅₀/ml.

Experimental design. Three to 4-week-old ICR mice were used in all experiments. Preparation and assay of RAMT serum have been described previously (4). Each group of at least 20 mice received intraperitoneal injections of 0.3 ml of either RAMT serum or normal rabbit serum (NRS) on days —6, —3, 0, 7plus;3, 7plus;6 and a dilution of HVH on day 0. The RAMT serum and NRS were free of anti-HVH activity by neutralization tests. Varying virus dilutions of HVH were inoculated by one of three routes: intracerebral, intraperitoneal, and intragenital. Methods for the last mode of inoculation have been reported earlier, infection being ascertained by recovery of the virus from the genitalia 3 days after inoculation (8).