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The Interferon System

Summary
The effect of interferon on expression of Epstein-Barr virus (EBV) early gene functions was investigated. The ‘early antigen’ synthesis which follows either EBV superinfection of established lymphoid cell lines or 5′-iododeoxyuridine activation of the intrinsic EBV genomes harboured by these cells could be suppressed with interferon. In contrast, the spontaneous early antigen expression that occurs in a few per cent of the cells in the producer cell lines could not be blocked with interferon.
The lymphoid cell lines tested differed in their ability to acquire an antiviral state after exposure to interferon. Several cell lines were also growth inhibited by the interferon preparations. The antiviral and growth inhibitory activities of different interferon preparations could not be separated by a number of criteria.

Sensitivity of the Epstein-Barr virus transformed human lymphoid cell lines to interferon.

A purified preparation of human leukocyte interferon used at this hospital in the treatment of malignant diseases was tested for its ability to modify the spontaneous cytotoxicity of peripheral lymphocytes from healthy donors. The inhibitory effect of allogeneic lymphocytes on the (3H)thymidine incorporation of a lymphoblastoid cell line, Raji, was augmented by the presence of interferon or by pretreatment of the lymphocytes with interferon. This form of pretreatment also increased lymphocytes' capacity for reducing the number of surface-adherent tumor cells in a microassay. Moreover, lymphocytes treated with interferon exhibited an enhanced cytotoxic capacity for target cells on incubation with such cells labelled with 51CR.

Interferon and spontaneous cytotoxicity in man. I. Enhancement of the spontaneous cytotoxicity of peripheral lymphocytes by human leukocyte interferon

Effect of interferon on exogenous, endogenous, and chronic murine leukemia virus infection

A study was undertaken in rabbits to determine how late in the course of keratoconjunctivitis caused by herpes simplex recovery could be effected by an inducer of interferon Interferon was induced by means of synthetic double-stranded RNA copolymer formed with polynosinic acid: polycytidilic acid RNA Therapy promotes recovery from severe and fully established keratoconjunctivitis for which treatment was begun as late as 3 days after virus inoculation No drug toxicity was observed in the therapeutic dose range These findings further support the proposed role of the interferon mechanism in the natural recovery of already established viral infection They also suggest the usefulness of interferon inducers in viral infections of man

Herpetic Keratoconjunctivitis: Therapy with Synthetic Double-Stranded RNA

SummaryDaily subcutaneous administration of concentrated preparations of crude or highly purified mouse brain interferon inhibited the multiplication of Friend virus and the development of splenomegaly in Swiss mice. Initiation of a continued interferon treatment 1 week after viral inoculation, at a time when splenic enlargement had already developed, still exerted a significant inhibitory effect on further development of splenomegaly. Interferon administration for only the 1st week after viral infection was ultimately ineffective. On histologic examination, far fewer foci of Friend cells were observed in the spleens of interferon treated mice than in the spleens of untreated mice. It was suggested that the inhibition of splenomegaly observed after repeated interferon administration was due to a continued inhibition of viral multiplication. Further evidence was presented that interferon itself was responsible for the inhibitory effects observed.

Interferon and Murine Leukemia. — IV. Futher Studies on the Efficacy of Interferon Preparations Administered after Inoculation of Friend Virus

INTERFERON has been most effective in vitro and in vivo when administered before viral inoculation, considerably less effective when inoculated at the same time as the challenge virus, and often ineffective after viral inoculation1–3. The necessity of pretreatment of cells or animals to obtain an anti-viral effect has raised doubts as to the value of interferon in the treatment of viral diseases4–5.

Interferon and Murine Leukaemia. III: Efficacy of Interferon Preparations administered after Inoculation of Friend Virus

SummaryVarious factors pertaining to the absence of interferon in the tissues of mice with Friend disease and the passive administration of interferon to mice with Friend disease have been investigated.The diffusion of interferon after intravenous and intraperitoneal inoculation has also been described. After intravenous inoculation the titer of interferon in the serum decreased markedly and interferon was recovered in the urine. Interferon inoculated intraperitoneally diffused from the peritoneal cavity into the circulation at a relatively constant rate and a significant level of interferon was maintained in the serum for as long as 5 hours.We gratefully acknowledge the excellent assistance of Mlle. Chantal Bourali and of Mlle. Marie-The rese Thomas.

R. Falcoff

Papers

Interferon and Murine Leukemia. — IV. Futher Studies on the Efficacy of Interferon Preparations Administered after Inoculation of Friend Virus

Interferon and Murine Leukaemia. III: Efficacy of Interferon Preparations administered after Inoculation of Friend Virus

Interferon and murine leukemia. II. Factors related to the inhibitory effect of interferon preparations on development of Friend leukemia in mice.