Disease relevance of Emv3

• DBA/2 mice carry a single endogenous ecotropic murine leukemia provirus, Emv-3 [1].
• In addition, most of the replication-competent viruses that were sequenced appeared to result from simple mutation of Emv-3 rather than recombination with other endogenous murine leukemia viruses [1].
• We characterized an infectious ecotropic retrovirus spontaneously expressed in aged DBA/2 mice, which carries the complete but defective Emv-3 [2].
• The results of this study conclusively demonstrated that Emv-3 is not causally associated with the development of DMBA-induced lymphomas in DBA/2J mice [3].
• A replication-competent, endogenous retrovirus from an aged DBA/2 mouse contains the complete env from Emv-3 and a novel gag partially related to AKT-8 [4].

High impact information on Emv3

• We report here the entire sequence for the gag gene of rv-DBA/2aged as well as the previously unsequenced 3' end of the Emv-3 gag gene [4].
• The previous report showed that a recombination which resulted in the replacement of Emv-3 gag sequences with gag sequences homologous to those found in the AKT-8 virus had taken place [4].
• To test this possibility, we compared lymphoma incidence after percutaneous DMBA treatment in DBA/2J-dv/dv mice, which carry two copies of Emv-3, with lymphoma incidence in DBA/2J-d+18J/d+18J mice, which lost both copies of Emv-3 by homologous recombination involving the long terminal repeat sequences [3].
• Comparison of the nucleotide sequence of the Emv-3 provirus with the sequence of the highly infectious Akv murine leukemia virus revealed three nucleotide differences within the gag coding region [5].
• Thus, it seems most likely that the defect of expression of the Emv-3 provirus is due to the presence of a proline is position 3 of the gag polyprotein, preventing the myristylation [5].

Biological context of Emv3

• An interspecific backcross between strains MEV and CAST/Ei yielded the following gene order and distances in centimorgans: Ldlr-18.8 +/- 5.6-Apoa-4-7.3 +/- 3.5-Mpi-1-10.2 +/- 3.9-Emv-3 or dilute [6].
• To begin to differentiate between these different control mechanisms, we molecularly cloned two endogenous ecotropic proviruses, Emv-3 and Emv-13, complete with flanking cellular DNA sequences [7].
• By site-directed mutagenesis, we showed that the defect of Emv-3 expression indeed is localized to codon 3 of the gag gene [5].
• Previous experiments involving DNA transfection and marker rescue analysis of molecularly cloned Emv-3 DNA suggested that Emv-3 carries a small defect(s) in the gag gene, not detectable by restriction enzyme mapping, that inhibits virus expression in vivo and in vitro [8].

Associations of Emv3 with chemical compounds

• 5-Iododeoxyuridine and 5-azacytidine, two potent inducers of ecotropic virus expression, are relatively ineffective at inducing Emv-3 expression [8].

Regulatory relationships of Emv3

• A murine leukemia virus expressed in aged DBA/2 mice is derived by recombination of the Emv-3 locus and another endogenous gag sequence [2].

Other interactions of Emv3

• Marker rescue experiments suggested that Emv-3 is defective in the gag region and Emv-13 is defective in p15E-U3 [7].
• Some recombinant ecotropic viruses contained sequences in the p15E-U3 region that were not derived from Emv-1 and Emv-3 but were found in recombinant polytropic HRS/J viruses [9].

Analytical, diagnostic and therapeutic context of Emv3

• Using a combination of approaches, including DNA sequencing, peptide mapping, and metabolic labeling of cells with [3H]myristate, we have demonstrated that the defect in Emv-3 most likely results from a single nucleotide substitution within the gene for p15gag that inhibits myristylation of the Pr65gag N terminus [8].
• The endogenous ecotropic provirus Emv-3 present in DBA/2 mice is poorly expressed in the animal, as well as in cell cultures [5].

References