Suppression of Established Friend Virus Leukemia by Statolon V. Reversal of Virus-Induced Immunodepression to Sheep Erythrocytes 1

Abstract

Statolon, an extract of the mold Penicillium stolonijerum containing a double stranded RNA mycophage, can convert a rapidly lethal Friend leukemia viral (FV) infection into a dormant one (1-5). One inoculation of statolon, administered when FV is disseminated throughout the body, induces interferon and FV-cytotoxic antibody thereby suppressing both virus and virus-transformed cells (2, 5). This suppression results in a long lasting clinical remission during which no infective Friend virions can be detected (1, 4). The FV genome is present however, as shown by the spontaneous emergence of FV leukemia late in the life of mice with dormant infections and by the leukemogenicity of spleen cells transferred from mice with dormant infections to normal mice (3).

Interferon production leads to suppression of FV replication, but by itself cannot completely suppress the disease; poly I:C and Newcastle disease virus can produce as much interferon as statolon, clear the blood of FV but cannot convert FV leukemia into a dormant infection (2).

Production of humoral antibody against both virus and virus transformed cells appears to be crucial for development of the FV-dormant state. Untreated FV leukemic mice have no demonstrable antibody and are considered immunosuppressed in this regard, although high titers of circulating virus may mask the presence of antibody. Numerous investigators have used the immune response to sheep erythrocytes (SRBC) to evaluate the immunocompetence of FV-infected mice (6, 10). These workers have demonstrated repeatedly that the response to this antigen in infected mice is severely depressed relative to normal levels.

In this report we describe preliminary investigations of immunological reactivity to SRBC in FV-infected and statolon-treated mice. Using the Jerne and Nordin assay for hemolytic antibody plaque forming cells (anti-SRBC PFC) (11), we found that statolon abrogates the FV-induced immunodepression of the anti-SRBC response.