Interferon (150 units/ml) was used to treat SC-1 and AKR-2B cells which were chronically infected with murine leukaemia virus (MuLV). This led to a 100-fold decrease in the amount of infectious virus released into the medium and a 10-fold decrease in the number of virus particles measured by the virion-associated reverse transcriptase assay. However, there was little change in the amount of cell-associated infectious virus, though nearly twice as many cell-associated virions were counted in electron micrographs. With both types of cells, interferon blocked MuLV replication at the post-budding stage, but it did not change the morphology of the particles produced or their content of virion 70S RNA.
Infectious virus assembled on the cell membranes of interferon-treated cells was less stable at 37°C than that grown in the absence of interferon. Release of infectious virus from interferon-treated cells was not inhibited by actinomycin D or cycloheximide, though both agents inhibited virus production in controls.
These results show that interferon inhibits MuLV replication through effects on virion assembly; these lead both to the formation of non-infectious particles and of fewer virions. Kinetic analysis further shows that interferon affects MuLV assembly rapidly and induction of an antiviral protein may not be required.
BilliauA.,
SorbisH.,
DesomerP.1973; Influence of interferon on virus particle synthesis in oncornavirus carrier line: evidence for a direct effect on particle release. International Journal of Cancer 1 2:646–653
BilliauA.,
EdyV. S.,
SorbisH.,
DesomerP.1974; Influence of interferon on virus-particle synthesis in oncornavirus-carrier cell lines. II. Evidence for a direct effect on particle release. International Journal of Cancer 14:335–340
BilliauA.,
EdyV. G.,
DeclercoE.,
HeremansH.,
DesomerP.1975; Influence of interferon on the synthesis of virus particles in oncornavirus-carrier cell lines. III. Survey of effects on A-, B- and C- type oncornaviruses. International Journal of Cancer 15:947–953
BilliauA.,
HeremansH.,
AllenP. T.,
Demaeyer-GuignardJ.,
DesomerP.1976a; Trapping of OnCOT-navirus particles at the surface of interferon-treated cells. Virology 73:537–542
BilliauA.,
HeremansH.,
AllenP. T.,
DesomerP.1976b; Influence of interferon on the synthesis of virus particles in oncornavirus-carrier cell lines. IV. Relevance to the potential application of interferon in natural infectious diseases. Journal of Infectious Diseases 133: (Suppl.) A54–A55
FriedmanR. M.,
ChangE. H.,
RamseurJ. M.,
MyersM. W.1975; Interferon-directed inhibition of chronic murine leukemia virus production in cell cultures: lack of effect on intracellular viral markers. Journal of Virology 16:569–574
FriedmanR. M.,
RamseurJ. M.1974; Inhibition of murine leukemia virus production in chronically infected AKR cells: a novel effect of interferon. Proceedings of the National Academy of Sciences of the United States of America 71:3542–3544
HartleyJ. W.,
RoweW. P.1975; Clonal cell lines from a feral mouse embryo which lack host range restrictions for murine leukemia viruses. Virology 65:128–134
LevinJ. G.,
GrimleyP. M.,
RamseurJ. M.,
BerezeskyI. K.1974; Deficiency of 60 to 70S RNA in murine leukemia virus particles assembled in cells treated with actinomycin D. Journal of Virology 14:152–161
LevinJ. G.,
RosenakM. J.1976; Synthesis of murine leukemia virus proteins associated with virions assembled in actinomycin D-treated cells: evidence for persistence of viral messenger RNA. Proceedings of the National Academy of Sciences of the United States of America 73:1154–1158
MalechH. L.,
WivelN. A.1976; Properties of murine intracisternal A particles. Electron microscopic appearance after critical point drying and platinum shadowing. Virology 69:802–809
PalmiterR. D.1974; Magnesium precipitation of ribonucleoprotein complexes. Expedient techniques for the isolation of undegraded polysomes and messenger ribonucleic acid. Biochemistry 17:3606–3615
PithaP. M.,
StaalS. P.,
BolognesiD. P.,
DennyT. P.,
RoweW. P.1977; Effect of interferon on murine leukemia virus infection. II. Synthesis of viral components in exogenous infection. Virology 79:1–13
PithaP. M.,
StaalS. P.1978; Effect of interferon on murine leukemia virus infection. III. Effect of interferon on MSV induced transformation. Virology 90:151–155
RoweW. P.,
HartleyJ. W.,
LanderM. R.,
PughW. E.,
TeichN.1971; Noninfectious AKR mouse embryo cell lines in which each cell has the capacity to be activated to produce infectious murine leukemia virus. Virology 46:866–867
SvobodaJ.,
ChyleP. P.,
SimkovicD.,
HilgertT.1963; Demonstration of the absence of infectious Rous virus in rat tumor XC, whose structurally intact cells produce Rous sarcoma when transferred to chick. Folia Biologica Prague 9:77–81
SwetlyP.,
OstertagW.1974; Friend virus release and induction of hemoglobin synthesis in ery-throleukemia cells respond differently to interferon. Nature, London 251:642–644
TaylorJ.1965; Studies on the mechanism of action of interferon. Interferon action and RNA synthesis in chick embryo fibroblasts infected with Semliki Forest virus. Virology 25:340–349
Van GriensvenL. J. D. L.,
BaudelaireM. C.,
PeriesJ.,
Em Anoel-R A VicovitchR.,
BoironM.1971 In Biology of Oncogenic Viruses vol 2 pp 145–153 Lepetit Colloquia on Biology and Medicine Amsterdam: North-Holland;
WivelN. A.,
SmithG. H.1971; Distribution of intracisternal A-particles in a variety of normal and neoplastic mouse tissues. International Journal of Cancer 7:167–175
WongP. K. Y.,
MacleodR.1975; Studies on the budding process of a temperature-sensitive mutant of murine leukemia virus with a scanning electron microscope. Journal of Virology 16:434–442
WongP. K. Y.,
YuenP. H.,
MacleodR.,
ChangE. H.,
MyersM. W.,
FriedmanR. M.1977; The effect of interferon on de novo infection of Moloney murine leukemia virus. Cell 10:245–252