Mechanism of chemical activation of expression of the endogenous ecotropic murine leukemia provirus Emv-3

J. A. Mercer, K. H. Lee, B. A. Nexo, N. A. Jenkins, N. G. Copeland

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

DBA/2 mice carry a single endogenous ecotropic murine leukemia provirus, Emv-3. This provirus is defective; it is very poorly expressed in young DBA/2 mice. The defect in Emv-3 is caused by a single base substitution in codon 3 of p15gag The resulting amino acid substitution inhibits myristylation of the gag precursor and subsequent virus assembly. Despite this defect, percutaneous treatment of DBA/2 mice with the carcinogen and mutagen 7,12-dimethylbenz[a]anthracene (DMBA) induces ecotropic marine leukemia virus replication in virtually all treated mice. We hypothesized that this induction is the result of a DMBA-induced reverse mutation in codon 3 of p 15gag which allows for efficient myristylation. We tested this hypothesis by isolating ecotropic viruses from DMBA-treated mice and determining the DNA sequences of selected regions of p 15gag, including codon 3. In support of the above-described model, all of the viruses examined contained single nucleotide substitutions in codon 3. 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. These studies may provide a basis for development of a sensitive assay for the mutagenic activity of a variety of chemical carcinogens in vivo.

Original languageEnglish (US)
Pages (from-to)2245-2249
Number of pages5
JournalJournal of virology
Volume64
Issue number5
DOIs
StatePublished - 1990

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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