Effect of Interferon on Murine Leukaemia Virus Infection. IV. Formation of Non-infectious Virus in Chronically Infected Cells

Abstract

SUMMARYInterferon (I5O units/ml) was used to treat SCq and AKR-2B cells which were chronically infected with murine leukaemia virus (MuLV). This led to a Ioo-fold decrease in the amount of infectious virus released into the medium and a Io-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 cellassociated 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 7oS 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.

Innate antiviral response targets HIV-1 release by the induction of ubiquitin-like protein ISG15

“…HIV-1 virions assembled in IFN-treated T cells show a low infectivity, accumulate at the plasma membrane, and have altered morphogenesis (29)(30)(31). Similar defects were seen in IFN-treated cells infected with murine leukemia virus (32). We have shown that IFN-␣-and IFN-␤-mediated inhibition correlates with the induction of ISG15 (33).…”

Biochemical Analysis and Electron Microscopic Study on Intracellular Virions in NIH/3T3 Mouse Cells Chronically Infected with Moloney Murine Leukaemia Virus: Effect of Interferon

“…An alternative possibility is that the vacuolar virions are a result of self phagocytosis by the cells of virus particles which are still bound to their own surface. The higher number of vacuolar virions found in IFN-treated cells does not contradict this possibility since several studies (Billiau et al, 1976;Chang & Friedman, 1977;Pitha et al, 1979b) have illustrated an accumulation of membrane-bound virions in IFN-treated cells. However, although this possible mechanism cannot be totally excluded, it seems rather unlikely, because careful analysis of many sections of IFN-treated and untreated cells revealed that virions bound to the cell surface are quite rare in our system.…”

Molecular Targets for AIDS Therapy

“…Interferon-a (IFN-a) is thought to affect this budding process as well as several late events in the replicative cycle, and this agent is active against HIV in vitro during acute infection (85). 1538 Studies of murine retroviruses indicate that interferons predominantly affect the late stages of virion release from the plasma membrane of chronically infected cells (86). Indeed, IFN-a suppresses the production or release of HIV virions in chronically infected cells, but has no effect on the amount ofcell-associated viral proteins (87).…”