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Generation of mink cell focus-forming viruses by Friend murine leukemia virus: recombination with specific endogenous
Abstract:
A family of recombinant mink cell focus-forming viruses (MCF) was derived by inoculation of NFS mice with a Friend murine leukemia virus, and their genomes were analyzed by RNase T1-resistant oligonucleotide fingerprinting. The viruses were obtained from the thymuses and spleens of preleukemic and leukemic animals and were evaluated for dualtropism and oncogenicity. All these isolates induced cytopathic foci on mink cells but could be classified into two groups based on their relative infectivities for SC-1 (mouse) or mink (ATCC CCL64) cells. One group of Friend MCFs (F-MCFs) (group I) exhibited approximately equal infectivities for SC-1 and mink cells, whereas a second group (group II) infected mink cells 1,000- to 10,000-fold more efficiently than SC-1 cells. Structural analyses of the F-MCFs revealed that group I and group II viruses correlated with recombination of Friend murine leukemia virus with two distinct, but closely related, endogenous NFS proviral sequences. No correlation was found between the type of F-MCF and the tissue of origin or the disease state of the animal. Furthermore, none of the F-MCF isolates were found to be oncogenic in NFS/N or AKR/J mice. F-MCFs of both groups underwent extensive substitution of ecotropic sequences, involving much of the gag and env genes of group I F-MCFs and most of the gag, pol, and env genes of group II F-MCFs. All F-MCF isolates retained the 3' terminal U3 region of Friend murine leukemia virus. Comparison of the RNAs of the F-MCFs with RNAs of MCFs derived from NFS.Akv-1 or NFS.Akv-2 mice indicated that the F-MCFs were derived from NFS proviral sequences which are distinct from the sequences contained in NFS.Akv MCF isolates. This result suggested that recombination with particular endogenous proviral sequences to generate MCFs may be highly specific for a given murine leukemia virus.
Insights
Researchers studied recombinant mink cell focus-forming viruses (MCFs) from Friend murine leukemia virus in mice. They found distinct viral groups based on cell infectivity, linked to specific endogenous proviral sequences, but none were oncogenic.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- Murine leukemia viruses (MLVs) can recombine with endogenous retroviruses to form mink cell focus-forming viruses (MCFs).
- MCFs are often found in leukemic mice and are associated with lymphomagenesis.
- Understanding MCF generation and properties is crucial for deciphering MLV-induced leukemogenesis.
Purpose of the Study:
- To characterize the genomes and biological properties of recombinant Friend murine leukemia virus-derived MCFs (F-MCFs).
- To investigate the relationship between F-MCF genetic structure, cell tropism, and oncogenicity.
- To determine the origin of endogenous sequences involved in F-MCF formation.
Main Methods:
- Derivation of F-MCFs from Friend MLV-inoculated NFS mice.
- Analysis of viral genomes using RNase T1-resistant oligonucleotide fingerprinting.
- Evaluation of viral infectivity for mouse (SC-1) and mink (ATCC CCL64) cells.
- Assessment of oncogenicity in NFS/N and AKR/J mice.
Main Results:
- F-MCFs could be classified into two groups based on differential infectivity for mink versus mouse cells.
- Group I F-MCFs showed similar infectivity for both cell types, while Group II infected mink cells significantly more efficiently.
- Genomic analysis revealed distinct endogenous NFS proviral sequences recombined with Friend MLV to form Group I and Group II F-MCFs.
- No correlation was found between F-MCF type and tissue origin or disease state.
- None of the generated F-MCF isolates demonstrated oncogenicity in susceptible mouse strains.
Conclusions:
- F-MCF generation involves recombination with specific endogenous NFS proviral sequences, defining distinct viral groups.
- The observed tropism differences are linked to the specific endogenous sequences involved in recombination.
- The lack of oncogenicity in these specific F-MCF isolates suggests that other factors may contribute to Friend MLV-induced leukemogenesis.
