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Published on: December 31, 2014
Transformation by murine sarcoma virus alters the sensitivity of clonal cells derived from NIH/3T3 mouse fibroblasts
Abstract:
In contrast to normal clonal cells (A5) derived from NIH/3T3 mouse fibroblasts, another clone (A10) derived from the same source was found to be resistant to the anti-lytic-virus activity of IFN and to be deficient in the induction of (2'-5') oligoadenylate synthetase (2-5A synthetase) by IFN. Following infection of either A5 or A10 cells with Moloney murine sarcoma virus (MSV), a few transformed colonies were isolated, expanded, and tested for their sensitivity to IFN. It is clearly demonstrated that IFN exerts a specific anti-proliferative effect on both MSV-transformed A5 (MA5) and A10 (MA10) cells, as evident by a slower growth rate, a decreased rate of DNA synthesis, and a lower cloning efficiency in its presence. Furthermore, unlike the original A10 cells, the IFN-treated transformed counterpart (MA10 cells), as well as MA5 cells, were protected from the lytic effect of either mengovirus or vesicular stomatitis virus (VSV). In addition, IFN treatment inhibited the release of retroviral particles from the transformed cells. The level of 2-5A synthetase activity in the various transformed cell lines was then determined. Whereas in A10 cells an induction of less than twofold in the enzymatic activity was detected following IFN treatment, a four- to fivefold increase in this activity could be seen in MA10 cells.
Insights
Interferon (IFN) shows anti-proliferative effects on virus-transformed mouse cells. IFN treatment restores antiviral activity and enhances 2-5A synthetase induction in these cells.
Area of Science:
- Cell Biology
- Virology
- Immunology
Background:
- NIH/3T3 mouse fibroblasts yield clones with differing sensitivities to interferon (IFN).
- Clone A10 is resistant to IFN's anti-lytic-virus activity and deficient in IFN-induced (2'-5') oligoadenylate synthetase (2-5A synthetase).
Purpose of the Study:
- To investigate the effects of IFN on Moloney murine sarcoma virus (MSV)-transformed mouse fibroblast clones (A5 and A10).
- To assess IFN's impact on cell proliferation, antiviral state, and 2-5A synthetase activity in transformed cells.
Main Methods:
- MSV infection of A5 and A10 cells to generate transformed cell lines (MA5 and MA10).
- Treatment of normal and transformed cells with IFN.
- Assessment of cell growth rate, DNA synthesis, cloning efficiency, and sensitivity to mengovirus and vesicular stomatitis virus (VSV).
- Measurement of 2-5A synthetase activity.
Main Results:
- IFN exhibited specific anti-proliferative effects on both MA5 and MA10 cells, reducing growth rate, DNA synthesis, and cloning efficiency.
- IFN-treated MA5 and MA10 cells, unlike original A10 cells, were protected from viral lysis by mengovirus and VSV.
- IFN treatment inhibited retroviral particle release from transformed cells.
- IFN induced a four- to fivefold increase in 2-5A synthetase activity in MA10 cells, compared to a less than twofold increase in A10 cells.
Conclusions:
- IFN exerts significant anti-proliferative and antiviral effects on MSV-transformed mouse fibroblasts.
- IFN treatment can restore antiviral defense mechanisms, including 2-5A synthetase induction, in transformed cells.
- These findings highlight the potential of IFN in controlling viral infections and cellular transformation.
