Introduction of a cis-Acting Mutation in the Capsid-Coding Gene of Moloney Murine Leukemia Virus Extends Its Leukemogenic Properties

作者: Muriel Audit , Jérôme Déjardin , Barbara Hohl , Christine Sidobre , Thomas J. Hope

DOI: 10.1128/JVI.73.12.10472-10479.1999

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

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