[The antiproliferative effects associated with vincristine and human interferons in experimental in vitro systems]. / Effets antiprolifératifs associés du vincristine et des interférons humains dans des systèmes expérimentaux in vitro.

Cytotoxic potential of suboptimal doses of vincristine associated with human interferon was studied in two cell lines of tumoral origin, as compared to the action of or gamma type interferon preparations. Results show that the vincristine cytotoxic effect may be synergistically augmented in both culture types by simultaneous interferon administration.

[Gamma interferon induced in human leukocytes by phytohemagglutinin: its production and biological characteristics]. / Inteféron gamma induit dans des leucocytes humains par la phytohémagglutinine: production et carcatéristiques biologiques.

Human gamma type interferon (IFN) preparations were obtained through phytohemagglutinin stimulation of leukocytes from the peripheral blood. Biological value of these preparations varied between 160 u and 800 u/ml, depending on leukocyte incubation medium, culture system and inductor conservation. The rising of the antiviral activity through association between gamma (3 u) and alpha (27 u) interferons was revealed by the virus quantity reduction (in this case the vesicular stomatitis virus was used) during a 24-hour multiplication cycle. The protection ensured by the mixture of the two types of interferon was about ten times higher than the additive effect of the two preparations. Study of the antiproliferative activity of a gamma interferon preparation was conducted on two human cell lines of tumoral origin (T-10 from a glioblastoma, and HEp-2) and revealed the difficulties to quantify precisely this property of the crude gamma interferon preparations.

[Anti-proliferative and antiviral effects of human alpha-interferon on tumor cells]. / Effets antiprolifératif et antiviral de l'interféron humain du type alpha sur des cellules tumorales.

Antiproliferative and antiviral activities of a type alpha human leukocytic interferon on several heteroploidic cell lines: HeLa, HEp-2, and T-10, a cell line of malignant origin (glioblastoma) were investigated, as compared to subcultures of human embryo fibroblasts. The tumor cell multiplication rate decreased proportionally to the amount of interferon in the culture medium. The highest interferon concentration used in our experiments (1,000 mu/ml) induced a decrease of the normal cell multiplication rate (human embryo fibroblasts). The same amount of interferon had a cytotoxic effect against the T-10 cells, but this phenomenon is reversible if the interferon is excluded after 24 h from the culture medium. There was no quantitative relation between the magnitude of the antiviral and of the cytotoxic effects of the type alpha human interferon on the tested cellular substrates.

Investigation of humoral and cell-mediated immunity aspects in mice with experimental latent herpes infection.

An experimental latent herpes infection was established by intradermal inoculation of the mouse ear or of the footpad with a wild strain and a temperature-sensitive (ts) mutant of herpes virus type 2. The wild strain was latency-positive irrespective of the inoculation site; the ts mutant induced latent ganglionic infection only when inoculated in the footpad. Neutralizing antibodies could be detected only after inoculation of the wild strain. The establishment of latency was not prevented by the presence of either a humoral or a cell-mediated immune response.

Effect of interferon on virus-transformed and tumor cell lines.

The cell growth inhibitory action of rat interferon (IFN) was investigated in two systems: a cell line obtained by transformation of rat embryo fibroblasts under the action of a ts mutant of herpes simplex virus and a tumor cell line derived from tumors induced in rats by transformed cells. The growth inhibitory effect of IFN, evaluated by cell counting and colony formation in soft agar medium, was dependent on the exponential cell growth rate and on the concentration of IFN in the medium. Long-time subcultivation of the two cell lines in the presence of IFN did not result in the selection of a cell population resistant to the growth inhibitory effect of IFN, but led to a decrease in the oncogenic potency of the tumor cell line.

Investigation of the effect of cellular and viral nucleic acids on certain virus infections. Note 2. Effect of nucleic acids on virus multiplication in cell cultures.

Treatment of cell cultures with different natural nucleic acids prior to inoculation of herpes simplex virus type 1 led in certain cases to an obvious reduction in infectant titer. The reduction was maximum at a dose of 50 micrograms nucleic acid/culture tube and it was not dependent on the nature of the nucleic acid preparation. The antiviral effect of nucleic acids was enhanced by complexation with intercalation agents such as ethidium bromide or violamycin BI. No detectable amounts of interferon could be made evident in cell cultures treated with chromosomal DNA under conditions leading to a reduction by 1.75 log in infectant titer.

Investigations in the transforming activity of temperature-sensitive mutants of herpes simplex virus.

Transformation of rat embryo fibroblast was induced by a temperature-sensitive mutant of herpes simplex virus type 2. Transformation was scored using the morphological criterion of focus formation and the cell changes that lead to the final focus are described. Virus genome persistence in the transformed cell line was demonstrated by the presence of virus-specific membrane antigens and by the specificity of antibodies elicited in rabbits by inoculation of transformed cells. The cytogenetic analysis of the transformed cells revealed changes in chromosome number and the presence of marker chromosomes.

Persistent measles virus infection in a calf kidney cell line. Note I. Establishment of calf kidney cell lines chronically infected with measles virus and some of their biological characteristics.

Several types of persistent measles virus infection resulting in lytic infections could be established in a calf kidney cell line, according to the passage level of the substrate and to the virus strain inoculated. Persistent measles virus infection in calf kidney cells was characterized by the limited proportion of infected cells, the large amount of infectant virus, and the alteration of morphological and growth characteristics of the cells. The mechanism of this persistent infection is discussed.

Investigations of the antiviral activity of some nitroso-urea derivatives. Inhibitory action of the IOB-252 nitroso-urea derivative on vaccinia virus incell cultures.

The nitroso-urea derivative IOB-252 was administrered in monkey kidney cell cultures in a concentration of 40 mug/ml 24 hours before inoculation of vaccinia virus and maintained afterwards in a concentration of 25 mug/ml. The drug inhibited vaccinia virus multiplication, hemagglutinin synthesis and late cytopathic effect, but did not prevent early cytopathic lesions. IOB-252 inhibited the synthesis of interferon initiated by a viral inductor and blocked the antiviral effect of an exogeneous interferon. The mechanism of action of the drug is discussed.

The formation of virus polyribosomes in L cells infected with vaccinia virus.

The fate of early virus messenger RNA in the cytoplasm of vaccinia-infected L cells has been studied during the first hour after infection. The RNA is made in the virus core structure from which it is rapidly released. It accumulates in the polyribsome fraction, where at least 75% is bound to ribosomes through an EDTA-sensitive link. Three distinct structures have been identified as possible intermediates in virus polyribosome formation. The first is a ribonucleoprotein complex (RNP) in which virus RNA is associated with cellular proteins. A complex having apparently similar properties, is formed when virus RNA is added to a cytoplasmic extract in vitro. The other two structures may consist of an RNP moiety associated with the small ribosomal subunit, or with a single ribosome. At least part of the RNA isolated as RNP appears to be a precursor of the virus messenger found in polyribosomes.

The presence of interferon and type A immunoglobulins in the nasopharyngeal secretions of volunteers immunized with an inactivated influenza vaccine.

The presence of interferon and type A immunoglobulins (IgA) was followed up in the nasopharyngeal washings collected from volunteers immunized intranasally with an inactivated influenza vaccine [strain A/Rom 1/73 (H3N2)]. Interferon was detected 24 hours after vaccine administration, its incidence being similar to that in the course of acute infection. Intranasal administration of inactivated influenza vaccine stimulated the production of secretory IgA in 3 of 10 samples collected 12 days after vaccination. At the same time, IgA were found in 4 samples collected before vaccination, and inhibited in certain cases the stimulation of interferon synthesis. The practical importance of the route of influenza vaccine administration is discussed.

The effect of interferon on the formation of virus polyribosomes in L cells infected with vaccinia virus.

The effect of interferon treatment of mouse L cells on the fate of virus messenger RNA following infection with vaccinia virus has been studied. The polyribosomes of interferon-treated, infected cells are found to be disaggregated and it is proposed that htis results from inhibition of the initiation of virus polypeptide snythesis. Evidence is presented that inhibition of polypeptide chain elongation also occurs. The block in initiation appears to be due to the failure of the small ribosome subunit to attach to the virus messenger ribonucleoprotein complex. The translation of the different vaccinia messenger species is inhibited to a comparable extent.