Jean-Claude Guillon

Chronic production of interferon in carrier mice congenitally infected with lymphocytic choriomeningitis virus

Abstract Congenital infection of mice with lymphocytic choriomeningitis virus leads to a lifelong virus carrier state. Here we provide evidence for the presence and action of interferon in such mice. The level of circulating interferon in adult carrier mice is 8–16 NIH units/ml of plasma. This interferon is acid stable and is capable of inducing 2–5A synthetase in mouse L 929 cells but not in human HeLa cells. Control, noinfected mice show less than 1 NIH unit/ml of plasma. In accord with these results, adult carrier mice have higher levels of the interferon-mediated pppA(2′p5′A)n synthetase (2–5A synthetase) in their liver and spleen than normal mice. Congenitally infected newborn mice also have higher levels of 2–5A synthetase in their liver in contrast to newborn control mice. These results in congenitally infected newborn and adult mice suggest that interferon may play a role, at least in part, in the pathogenesis of infection.

Protein kinase (pp67-IFN) in plasma and tissues of mice with high levels of circulating interferon

Summary Interferon-treated mouse cells show an enhanced protein kinase activity which is manifested by the phosphorylation of an endogenous 67,000-MW phosphoprotein (pp67-IFN). This kinase activity can be assayed conveniently and efficiently after its partial purification on poly(I)poly(C)-Sepharose. Here we show that besides cell tissue cultures, the pp67-IFN kinase is also detectable in the liver, spleen and plasma of mice injected with Newcastle disease virus (NDV), encephalomyocarditis virus (EMCV), poly(I)poly(C) or poly(A)poly(U), all of which induce interferon. In addition to the pp67-IFN kinase, we studied the level of pppA(2′p5′A)n synthetase (2–5A synthetase) in the spleen and liver of mice in order to monitor the action of circulating interferon. In contrast to a previously published work, no 2-5A synthetase was detectable in the plasma or in the serum of mice which showed high levels of 2–5A synthetase in their liver and spleen. The kinetics of enhancement of pp67-IFN kinase in the plasma and in the spleen followed that of circulating interferon. The maximum levels of this enzyme in mice were 15–18 h after the peak of circulating interferon. The pp67-IFN from the plasma and spleen of mice and from interferon-treated mouse cells were phosphorylated in their serine and threonine residues. The function of the kinase in the plasma of mice with high levels of circulating interferon remains to be investigated. Its detection, however, may serve as a marker for the presence and action of interferon since the pp67-IFN kinase could be detectable at a time when the level of circulating interferon is diminished.

Rapid enrichment of mouse natural killer cells by use of wheat germ agglutinin

The separation of mouse T and B lymphocytes by differential agglutination with wheat germ agglutinin (WGA) also enriches natural killer (NK) activity 2-7-fold. NK cells are recovered within the agglutinated cell population indicating that NK cells bind WGA. This technique can be applied to endogenous or interferon-induced NK cells.

Evidence for the presence of T lymphocytes mediating lymphocytic choriomeningitis virus-specific delayed-type hypersensitivity in meningeal infiltrates of infected mice

Summary Meningeal infiltrates from mice infected during a period of 7 to 8 days with lymphocytic choriomeningitis virus contained T lymphocytes which mediated a virus-specific delayed-type hypersensitivity reaction upon local adoptive transfer. These preliminary results suggest that such a T-lymphocyte function may intervene in the pathogenesis of this viral infection.

Beneficial use of cyclosporin a in lymphocytic choriomeningitis virus infection in mice: Dose and kinetic effects

Summary The dose effect and the kinetics of cyclosporin A (CSA) injection in the course of lymphocytic choriomeningitis viral infection were studied. Several doses and different timings were exploited and it was found that, for maximal protection of lethally infected mice, CsA should be administered at a dose of 100 mg/kg on days 0 and 1 post-infection.

Prévention par les globulines anti-interféron de la mortalité des souris infectées par le virus de la chorioméningite lymphocytaire: Prevention of death in mice fatally infected with lymphocytic choriomeningitis virus by anti-interferon globulins

Summary Intracerebral inoculation of adult mice with lymphocytic choriomeningitis (LCM) virus is lethal, and is considered to be due to the development of sensitized T lymphocytes which are cytotoxic for virus-infected host cells. Injection of sheep anti-mouse interferon globulin into LCM virus-infected mice resulted in a 100 to 1,000-fold increase in viral titres, a 10 to 100-fold increase in serum interferon titres and the survival of virtually all of the mice. Anti-interferon globulin-treated mice also showed a focal necrosis of spleen and lymph nodes and a depletion of thymic lymphocytes. These lesions were more marked than in the organs of LCM virus-infected mice injected with normal sheep serum. The increased amounts of virus and/or interferon in mice injected with anti-interferon globulin and the marked lesions in these lymphoid organs may depress the immune response and thus be related to the survival of virus infected mice.

Infection du souriceau nouveau-né par le virus de la chorioméningite lymphocytaire: Rôle de la souche de virus et cas de l'infection congénitale

Summary Infection of newborn mice at birth (neonatal infection) by lymphocytic choriomeningitis virus (LCMV) leads to an acute syndrome characterized by inhibition of growth, liver cell degeneration and death in the first few weeks of life. We have previously shown that interferon induced after neonatal infection is responsible in large part for this early acute syndrome. In this paper we showed that such an early acute syndrome observed after neonatal infection was not restricted to infection by the Institut Pasteur strain of LCMV (CIPV-76001) since a similar syndrome is observed with two different Armstrong strains of LCMV. In utero infection of mice with LCMV (congenital infection) led to a carrier state without any apparent symptom. It was not possible to detect interferon in the plasma of such mice which showed high virus titres. Nevertheless, infection of newborn mice with LCMV originated from congenitally carrier mice led to an early acute syndrome with a variable mortality which was correlated with the level of circulating interferon. The present results bring another example of the role of interferon in the pathogenesis of infection of newborn mice with LCMV.