Relationship of Friend murine leukemia virus production to growth and hemoglobin synthesis in cultured erythroleukemia cells

Abstract

The factors that control oncornavirus formation were analyzed in Friend leukemia cells that undergo hematopoiesis when treated with dimethyl sulfoxide. Suspension cultures of Ostertag FSD-1 cell line were found to enter a G,, or resting state at the end of their proliferative phase and to simultaneously cease producing helper and dependent components of Friend virus. Whereas the decline in virus production is at least 100-fold, rates of cellular RNA and protein synthesis are only slightly lower in resting than in growing cells. Both resting and growing cells contain similarly large concentrations of the viral proteins P(30) and P(12). Dimethyl sulfoxide induces hemoglobin synthesis in growing cells, but its effects on virus production appear to be indirect results of its action to inhibit cell growth and thus to delay entry of cells into the Gn resting state. Furthermore, variant cell lines were obtained with differing abilities to synthesize virus or hemoglobin. Some lines no longer produce infectious virus, although they all harbor murine leukemia virus genes which are expressed to varying extents. The major internal protein of these oncornaviruses, P(30), is

Virus production and hemoglobin synthesis in variant lines of dimethyl sulfoxide-treated Friend erythroleukemia cells

“…It should be mentioned that, when the growth of the DMSO-treated cultures coincides with that of the untreated controls, the RT activity peaks of each occur on the same day, revealing the readily apparent differences between the two in the level of the enzyme (10). This increase in viral enzyme activity confirms and extends the findings of inducer-stimulated virus production by electron microscopy (32) and by biological assays (5,15,37). The report that RT activity was reduced after DMSO treatment in an independently derived FL line, T3C12 (6), is in contrast to the report of Ikawa et al, who had developed that line.…”

“…In fact, budding was further enhanced on the cells growing in medium containing both DMSO and bromodeoxyuridine. Subsequently, it was found that differentiation could be stimulated in the treated cells of some lines whether or not they were producing virus (16,37,41).…”

Synthesis and Glycosylation of Polyprotein Precursors to the Internal Core Proteins of Friend Murine Leukemia Virus

“…Several studies have indicated that cultured cells infected with MuLV release infectious virions only during periods of active growth and cease virus production in the Go state of proliferative arrest (15,16,20). This also seems to be true of Eveline cells.…”

“…Stationary-phase Eveline cells were diluted into fresh growth medium containing L-['4C]leucine (New England Nuclear Corp.) in the amounts indicated in the figure legends. Samples taken subsequently were assayed for MuLV infectivity as described previously (20). For determination of radioactive virus release, samples of the medium were cleared of cells by low-speed centrifugation and layered onto tubes containing 25-ml linear gradients from 15 to 60% sucrose in TSE overlaid with 10 ml of 15% sucrose in TSE.…”

Immunotherapy of murine leukemia. VII. Prevention of friend leukemia virus‐induced immunosuppression by passive serum therapy

“…The growth of the suspension derivative of the FLV-infected Eveline STU mouse embryo cell line (denoted FES) has been described in detail elsewhere (Seifert et al, 1975;Collins et al, 1977), as has that of the related suspension derivative of Gross leukemia virus (GLV)-infected STU mouse embryo cells (GES) (Hunsmann et al, 1974;Collins et al, 1977). The suspension-grown , non-virus-producing FLV-erythroleukemia FLC-745 cell line, derived from the spleens of FLV-infected D B N 2 mice (Friend et al, 1966;Sherton et al, 1976), and the L5178Y DBA/2 methylcholanthrene (MCA)-induced lymphoma cell line (Law et al, 1949) were obtained from Dr. E.F. Wheelock, Jefferson Medical College, Philadelphia PA. The EL-4 C57BLi6 benzanthracene-induced lymphoma (Gorer and Amos, 1956), the YAC-1 Moloney leukemia virus-induced lymphoma of A/Sn mouse origin (Klein and Klein, 1964), the RBL-5 Rauscher leukemia virus (RLV)-induced lymphoma of C57BL/6 origin (Sato et al, 1973), and the radiation-induced RLd 1 BALBic lymphoma (McCoy et al, 1967) were obtained from Dr. Hillel Koren, Duke University Medical Center.…”