Poorly expressed endogenous ecotropic provirus of DBA/2 mice encodes a mutant Pr65(gag) protein that is not myristylated

N. G. Copeland, N. A. Jenkins, B. Nexo, A. M. Schultz, A. Rein, T. Mikkelsen, P. Jorgensen

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

DBA/2 mice carry a single endogenous ecotropic murine leukemia provirus designated Emv-3. Although this provirus appears to be nondefective by genomic restriction enzyme mapping, weanling mice do not produce virus and only about one-third of adult mice ever express virus. 5-Iododeoxyuridine and 5-azacytidine, two potent inducers of ecotropic virus expression, are relatively ineffective at inducing Emv-3 expression. However, the chemical carcinogen 7,12-dimethylbenz(a)anthracene can induce ecotropic virus expression in approximately 95% of treated DBA/2 mice. 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. 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 p15(gag) that inhibits myristylation of the Pr65(gag) N terminus. Myristylation of Pr65(gag) is thought to be required for this protein to associate with the plasma membrane and is essential for virus particle formation. These results provide a conceptual framework for understanding how Emv-3 expression is regulated during development and after chemical induction.

Original languageEnglish (US)
Pages (from-to)479-487
Number of pages9
JournalJournal of virology
Volume62
Issue number2
DOIs
StatePublished - 1988

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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