Genetic determinant of rapid-onset B-cell lymphoma by avian leukosis virus.
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 the region revealed a 42-nt deletion in EU-8 relative to LR-9, as well as some single-nucleotide changes. A mutant virus, delta LR-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.
Smith
M R
MR
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Smith
R E
RE
Dunkel
I
I
Hou
V
V
Beemon
K L
KL
Hayward
W S
WS
D000818:Animals; D001353:Avian Leukosis / Q000821:virology; D001354:Avian Leukosis Virus / Q000235:genetics* / Q000502:physiology; D001483:Base Sequence; D002642:Chick Embryo; D002874:Chromosome Mapping; D004279:DNA, Viral; D015750:Genes, gag; D016393:Lymphoma, B-Cell / Q000821:virology*; D008969:Molecular Sequence Data; D012326:RNA Splicing; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D013997:Time Factors
D004279:DNA, Viral