Pronounced antiviral activity of human interferon on bovine and porcine cells

Gresser, Ion; Bandu, Marie‐Thérèse; Brouty‐Boyé, Danièle; Tovey, Michaël G.

doi:10.1038/251543a0

Cited by 179 publications

(83 citation statements)

References 6 publications

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“…This suggests that proteolytic cleavage of the 21,000-dalton species could also be one of the origins for the genesis of the fast mobility species. Gresser et al (23) reported that Hu Le IF exhibits an antiviral activity on bovine cells much higher than that on human fibroblasts. This might indicate that the preparations used had a higher proportion of the modified species of Hu Le IF. We postulate that interferon, like many hormones and other multifunctional enzymes, has distinct domains assigned for separated functions: antiviral activity, species specificity, immune response, etc.…”

Section: Resultsmentioning

confidence: 99%

Human leukocyte interferon: Relationship between molecular structure and species specificity

Thang

Chelbi-Alix

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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Human leukocyte interferon can be separated into two classes of subspecies by polynucleotide-agarose affinity chromatography; 30-40% of the molecular species have the polynucleotide-binding property and 60-70% lack affinity for the polynucleotide ligand. When analyzed on sodium dodecyl sulfate/polyacrylamide gel electrophoresis, the former class of interferon has a slower mobility corresponding to the migration of a polypeptide of 21,000 daltons, while the latter class has a faster mobility corresponding to a polypeptide of 13,500-15,000 daltons. By analogy to the behavior of other interferons and a class of nucleotidyl transferases on the polynucleotide-agarose chromatography, we suggest that the human leukocyte interferon having the polynucleotide-binding site is in a possibly "native" conformation and the loss of affinity for polynucleotide results from a degradative alteration of the native molecules. Moreover, the alteration of interferon is accompanied by an increase in heterospecific activity on bovine cells. It is suggested that the polypeptide domain responsible for species specificity may be closely related to the polynucleotide binding area. The modified interferon molecule, however, still conserves its antiviral activity. The simplicity and the high capacity of polynucleotide-agarose chromatography make this a powerful technique for the purification of interferon. The easy separation of these two classes of human leukocyte interferon makes the purification procedures more rational and will facilitate the preparation of both subspecies to a high degree of molecular homogeneity. Human leukocyte interferon (Hu Le IF) contains two subpopulations of active molecules, which are differentiated by their molecular sizes, charge properties, and even biological activities (1-6). Such heterogeneity, resulting from the presence of molecular species having different physicochemical properties, complicates the purification of leukocyte interferon.In particular, the strategy for purification has been mostly orientated by the recovery of as much initial activity as possible, necessitating copurification of the two subpopulations.We have recently described an affinity chromatography with blue dextran or polynucleotide as ligand for proteins interacting with nucleic acids (7). Such chromatography not only allows the separation of proteins having a polynucleotide-binding site from other classes of proteins but also can be used to separate one native enzyme from a degraded enzyme that has lost the polynucleotide attachment site (7). The methodology was also applied to the characterization and purification of both viral and immune interferons (8-11). We postulate that the polynucleotide-binding property, observed with mouse types I and II and human interferons, could be a basic characteristic of this antiviral protein. This property also could reveal a structural homology between the mouse types I and II interferons (10). In this paper, we show that Hu Le IF can be separated into two classes of molecules according...

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Section: Resultsmentioning

confidence: 99%

Human leukocyte interferon: Relationship between molecular structure and species specificity

Thang

Chelbi-Alix

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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“…(d) The level of ( 2 ' -5')A,, i n intcrleron-treated cells, after virus infection, is sufficient to acti\:itc the RNase F [20]. (e) Introduction of (2'-5')A, into intact cells, by a variety of methods, has been accompanicd by an inhibition of cellular protein, RNA, and D N A synthesis, as well as inhibition of virus production Several reports have described cell lines which cannot be protected against viral infection by homologous interferon [19,23,24]. Characterization of the interferon-resistant mouse leukemia cell (L1210R) indicated that immune interferon induced an antiviral state, but fibroblast interferon did not [25].…”

Section: ~~ ~mentioning

confidence: 99%

A Mouse Cell Line, which Is Unprotected by Interferon against Lytic Virus Infection, Lacks Ribonuclease F Activity

Epstein

Czarniecki

Jacobsen

et al. 1981

European Journal of Biochemistry

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A mouse cell line, N I H 3T3, does not respond to some of the activities of interferon. Even after treatment with high concentrations of interferon the replication of lytic viruses, such as encephalomyocarditis virus (EMCV) and vesicular stomatitis virus (VSV) is not inhibited in these cells. In contrast, interferon treatment of these same cells results in the inhibition of Moloney murine leukemia virus (MMuLV) production. We have analyzed enzymatic pathways which are induced by interferon in these cells. After interferon treatment, the level of the (2'-5')oligoadenylate [(2'-5')A,] synthetase activity and the phosphorylation of the 67000-dalton protein (PI) are enhanced in NIH 3T3 cells to approximately the same level as interferon-sensitive mouse L-cells. Moreover, NIH 3T3 and L-cells contain approximately the same levels of enzymcs which inactivate (2'-5')A,. Both exogenously added (2'-5')Aj or double-stranded RNA (ds RNA) failed to inhibit protein synthesis in NIH 3T3 extracts even though they were potent inhibitors of L-cell extract-directed protein synthesis. Direct measurements of the (2'-S')A,-dependent ribonuclease F (RNase F) failed to detect such activity in NIH 3T3 cells. Our results, therefore, suggest that the presence of RNase F activity is necessary for the interferon-induced antiviral activity against EMCV and against VSV. The induction of protein kinase activity by interferon treatment of NIH 3T3 cells appears to have no direct effect on EMCV and VSV replication.

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“…By contrast, poor correspondence was seen between the antiviral titres of these supernatants using two different cell lines. The higher antiviral activity of human leukocyte IFN in bovine cells first noted by Gresser et al (1974) is probably primarily due to IFN-% which gives 10-to 20-fold higher titres than IFN-c~ 2 in bovine cells, compared with approximately sixfold lower titres on human amnion (WISH) cells (Weck et al, 1981). Despite this difference, after correction with a leukocyte IFN standard, geometric mean titres between the bioassays were not statistically different.…”

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confidence: 80%

Measurement of Interferon from in vitro Stimulated Lymphocytes by Bioassay and Monoclonal Antibody-based Immunoassay

Scott

Robinson

Secher

et al. 1985

Journal of General Virology

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SUMMARYPeripheral blood mononuclear cells (PBMC) derived from healthy individuals were stimulated with u.v.-inactivated Newcastle disease virus and the cell supernatants were assayed for both antiviral activity and alpha interferon (IFN-~) immunoreactivity. IFN-ct concentrations determined by two immunoradiometric assays (IRMAs) based on monoclonal antibodies that recognize different IFN-u subtypes correlated well together (r = 0.96) and with interferon concentrations determined by the two bioassays (r = 0-82 to 0.89), but the agreement between the results of the two bioassays was not as close (r = 0.79). As judged by the agreement between determinations on duplicate inductions of the same PBMC, the IRMAs were considerably more precise than the bioassays. Despite the use of a common IFN standard there were marked differences in the absolute titres of IFN determined by the IRMAs and bioassays, highlighting the difficulties in standardizing assays for IFN-u. The IRMA results suggest that there are no major differences in the spectrum of IFN-~ subtypes produced by healthy individuals under conditions of viral stimulation.In man, it is suggested that virus-induced interferon alpha (IFN-~) production is part of the innate immune response to natural virus infections. A multiplicity of genes code for different human leukocyte-derived IFN-u subtypes (Goeddel et al., 1981). A suspension of Namalwa lymphoblasts makes at least eight IFN-c( subtypes when stimulated with Sendai virus (Allen & Fantes, 1980) and it is likely that IFN-u derived from pooled buffy coat leukocytes consists of a similarly heterogeneous mixture. However, it is not clear whether an individual has the capacity to produce all IFN-~ subtypes and actually does so during a viral infection. The observation that some patients raise neutralizing antibodies to exogenous IFNs given for therapeutic purposes (Vallbracht et al., 1981 ;Mogensen et al., 1981, Trown et al., 1983 could be explained by the recognition of these exogenous IFN subtypes as 'foreign' proteins.In the present study, we set out to determine whether peripheral blood mononuclear cells (PBMC) from a number of healthy individuals produced different profiles of IFN-ct subtypes when stimulated by virus. In order to investigate this possibility, results obtained for each sample with two biological assays using two cell lines, and with two immunoradiometric assays (IRMAs) based on different monoclonal antibodies, were compared.Heparinized venous blood samples were obtained from healthy laboratory and hospital staff on one morning and were treated under identical conditions. Twenty-four individuals were tested on the first study day (sample 1). Four months later 16 of these individuals were available to give blood on the second study day (sample 2). PBMC were separated on Ficoll-Paque t Present address:

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Pronounced antiviral activity of human interferon on bovine and porcine cells

Cited by 179 publications

References 6 publications

Human leukocyte interferon: Relationship between molecular structure and species specificity

Human leukocyte interferon: Relationship between molecular structure and species specificity

A Mouse Cell Line, which Is Unprotected by Interferon against Lytic Virus Infection, Lacks Ribonuclease F Activity

Measurement of Interferon from in vitro Stimulated Lymphocytes by Bioassay and Monoclonal Antibody-based Immunoassay

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