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Unstable resistance of G mouse fibroblasts to ecotropic murine leukemia virus infection
Abstract:
G mouse cells were resistant to N- and NB-tropic Friend leukemia viruses and to B-tropic WN 1802B. Though the cells were resistant to focus formation by the Moloney isolate of murine sarcoma virus, they were relatively sensitive to helper component murine leukemia virus. To amphotropic murine leukemia virus and to focus formation by amphotropic murine sarcoma virus, G mouse cells were fully permissive. When the cell lines were established starting from the individual embryos, most cell lines were not resistant to the murine leukemia viruses. Only one resistant line was established. Cloning of this cell line indicated that the resistant cells constantly segregated sensitive cells during the culture; i.e., the G mouse cell cultures were probably always mixtures of sensitive and resistant cells. Among the sensitive cell clones, some were devoid of Fv-1 restriction. Such dually permissive cells, and also feral mouse-derived SC-1 cells, retained glucose-6-phosphate dehydrogenase-1 and apparently normal number 4 chromosomes. The loss of Fv-1 restriction in these mouse cells was not brought about by any gross structural changes in the vicinity of Fv-1 on number 4 chromosomes.
Insights
G mouse cells exhibit complex resistance patterns to various murine leukemia viruses. Most cell lines were sensitive, with resistant lines showing instability and segregation of sensitive cells.
Area of Science:
- Virology
- Genetics
- Cell Biology
Background:
- Murine leukemia viruses (MLVs) exhibit tropism, influencing host cell permissivity.
- The Fv-1 gene is a major determinant of resistance to certain MLVs in mice.
- Understanding MLV-host interactions is crucial for virology and retroviral research.
Purpose of the Study:
- To characterize the permissivity and resistance of G mouse cells to a panel of MLVs.
- To investigate the genetic basis of MLV resistance in G mouse cell lines.
- To determine if Fv-1 restriction is associated with chromosomal alterations.
Main Methods:
- Infection of G mouse cells with various N-, NB-, and B-tropic MLVs and murine sarcoma viruses.
- Focus formation assays to assess viral replication and cell killing.
- Cell line establishment from individual embryos and subsequent cloning.
- Analysis of Fv-1 restriction and chromosomal integrity in resistant and sensitive cell clones.
Main Results:
- G mouse cells showed differential sensitivity: resistant to N- and NB-tropic MLVs but permissive to amphotropic MLVs.
- Most established cell lines were sensitive to MLVs; only one resistant line was obtained.
- The resistant cell line continuously segregated sensitive cells, suggesting a mixed population.
- Some sensitive clones lacked Fv-1 restriction and retained normal chromosome 4 structure.
Conclusions:
- G mouse cells display a complex pattern of MLV tropism and Fv-1 restriction.
- MLV resistance in these cells is unstable and may involve a mixture of sensitive and resistant cell populations.
- Loss of Fv-1 restriction is not linked to gross structural changes near the Fv-1 locus on chromosome 4.