Introduction of a cis-acting mutation in the capsid-coding gene of Moloney murine leukemia virus extends its leukemogenic properties

Muriel Audit, Jérôme Déjardin, Barbara Hohl, Christine Sidobre, Thomas J. Hope, Marylène Mougel, Marc Sitbon*

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Inoculation of newborn mice with the retrovirus Moloney murine leukemia virus (MuLV) results in the exclusive development of T lymphomas with gross thymic enlargement. The T-cell leukemogenic property of Moloney MuLV has been mapped to the U3 enhaneer region of the vital promoter. However, we now describe a mutant Moloney MuLV which can induce the rapid development of a uniquely broad panel of leukemic cell types. This mutant Moloney MuLV with synonymous differences (MSD1) was obtained by introduction of nucleotide substitutions at positions 1598, 1599, and 1601 in the capsid gene which maintained the wild-type (WT) coding potential. Leukemias were observed in all MSD1-inoculated animals after a latency period that was shorter than or similar to that of WT Moloney MuLV. Importantly, though, only 56% of MSD1- induced leukemias demonstrated the characteristic thymoma phenotype observed in all WT Moloney MuLV leukemias. The remainder of MSD1-inoculated animals presented either with bona fide clonal erythroid or myelomonocytic leukemias or, alternatively, with other severe erythroid and unidentified disorders. Amplification and sequencing of U3 and capsid-coding regions showed that the inoculated parental MSD1 sequences were conserved in the leukemic spleens. This is the first report of a replication-competent MuLV lacking oncogenes which can rapidly lead to the development of such a broad range of leukemic cell types. Moreover, the ability of MSD1 to transform erythroid and myelomonocytic lineages is not due to changes in the U3 viral enhancer region but rather is the result of a cis-acting effect of the capsid-coding gag sequence.

Original languageEnglish (US)
Pages (from-to)10472-10479
Number of pages8
JournalJournal of virology
Volume73
Issue number12
DOIs
StatePublished - Dec 1999

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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