Production of interferon by human tumor cell lines

Abstract

Fourteen continuous human cell lines, including nine derived from tumors and five from non-neoplastic tissues, produced interferon in response to induction with bluetongue virus (BTV), Newcastle disease virus (NDV), and poly(I) . poly(C) complexed with DEAE-dextran. The seven best interferon-producing cell lines (one from a melanoma, five derived from carcinomas, and one SV40-virus-transformed kidney cell line) responded to at least one of the viral inducers with yields of interferon over 1000 units/ml. Because the HT-1376 bladder carcinoma cell line produced high yields of interferon in this survey, and is easily propagated, the optimal conditions for interferon production were investigated, using BTV as the inducer. Interferon yields in 59 inductions over a period of about two years consistently fell within a 6-fold range, and had a geometric mean titer of about 2700 reference units (RU)/ml, representing the production of about 3 RU/10(3) cells. This yield is comparable to mean titers of 1 to 10 RU/10(3) cells obtained by others with human leukocytes, foreskin cell strains, or the Namalva lymphoblastoid cell line. UV-inactivated BTV at a multiplicity corresponding to 10 PFU/cell was as effective an inducer in the HT-1376 cell line as the fully infectious virus at a multiplicity of 1 PFU/cell. The interferon produced by the HT-1376 epithelial cell line has characteristics similar to the interferon induced by poly(I) . poly(C) in human diploid fibroblasts. These studies clearly demonstrate that many different types of tumor-derived cells have the capacity to produce interferon, and that some equal or surpass the efficiency of diploid cells.

Sensing and Control of Bluetongue Virus Infection in Epithelial Cells via RIG-I and MDA5 Helicases

“…Interestingly, the IFN-␤ mRNA level was markedly high in A549 cells, as previously reported for these cells (22,23). Moreover, we described for the first time the underlying mechanisms leading to type I IFN production in nonimmune cells in response to BTV infection and identified the cellular sensors involved in this signaling cascade.…”

“…and then decreased at 24 h p.i., showing that this BTV-8 field strain has an intrinsic ability to induce IFN-␤ synthesis in its natural target cells. We then performed the same experiments with endothelial and epithelial cell lines of bovine (CPAE, MDBK) and human (A549) origins, the latter of which have been described as efficient IFN-␣/␤ producers in response to BTV infection (22,23). BTV-8 was able to replicate efficiently in these three cell lines ( Fig.…”

NS3 of Bluetongue Virus Interferes with the Induction of Type I Interferon

“…BTV is a strong inducer of IFN-I both in vivo and in vitro in multiple cell types derived from various tissues and species (26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Recently, we identified RIG-I and MDA5 helicases as sensors of BTV infection in nonhematopoietic cells and showed that these molecules displayed antiviral activities against the virus (26).…”

Production of high levels of human leukocyte interferon from a continuous human myeloblast cell culture

“…Stock cultures of KG-1 cells were incubated with 100 U of human leukocyte interferon per ml for 18 h at 37°C. NDV at 30 HA units/ml or Sendai virus at 200 HA units/ml was added to the cultures, and incubation was continued an additional 18 h. Culture fluids were harvested and assayed for interferon activity as described.…”

“…They are produced in vitro by various methods (11,14,17,18,29). Recently, the genes for human leukocyte and fibroblast interferon have been successfully integrated (24,38) into Escherichia coli plasmids and expressed (12,13,28).…”