Abstract: |
Infection of 10 day-old chicken embryos with the recombinant avian leukosis virus (ALV) EU-8 induces a high incidence of rapid-onset B-cell lymphoma by insertional activation of the c-myb gene. LR-9, a related ALV with differences from EU-8 in the gag and pol genes, induces rapid-onset lymphoma at only a low incidence. To localize the viral determinant(s) responsible for this biologic difference, we constructed and tested a series of reciprocal chimeras between EU-8 and LR-9 ALVs. The ability to induce rapid-onset lymphoma efficiently was localized to a 925-nucleotide (nt) region of the EU-8 gag gene. Sequence analysis of this region revealed a 42- nt deletion in EU-8 relative to LR-9, as well as some single-nucleotide changes. A mutant virus, ΔLR-9, constructed by deleting these 42 nt from LR- 9, also induced rapid-onset lymphoma at a high frequency, confirming the biologic significance of this deletion. This deletion removed nt 735 to 776, which lies within a cis-acting RNA element that negatively regulates splicing (NRS). The deletion was shown to cause an increase in splicing efficiency, which may lead to increased production of a truncated myb gene product from an ALV-myb readthrough RNA. |
Keywords: |
gene sequence; gene deletion; sequence deletion; mortality; nonhuman; animals; embryo; animal model; time factors; avian leukosis oncovirus; avian leukosis virus; b cell lymphoma; lymphoma, b-cell; molecular sequence data; recombination, genetic; base sequence; dna, viral; virus recombinant; oncogene c myb; rna splicing; chromosome mapping; virus carcinogenesis; sequence analysis, dna; chick embryo; chicken; genes, gag; priority journal; article; avian leukosis
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