Deletion of a GC-rich region flanking the enhancer element within the long terminal repeat sequences alters the disease specificity of Moloney murine leukemia virus.
Moloney murine leukemia virus (M-MuLV) is a replication-competent retrovirus which induces T-lymphoblastic lymphoma 2 to 4 months after inoculation. Enhancer sequences in the U3 region of the M-MuLV long terminal repeat, primarily the 75-bp tandem repeats, strongly influence the disease specificity and latency of M-MuLV. We investigated the role of GC-rich sequences downstream of the tandem repeats in the disease specificity of M-MuLV. A recombinant M-MuLV lacking 23 bases of a GC-rich sequence (-174 to -151), Delta 27A M-MuLV, was tested for pathogenesis in neonatal NIH Swiss mice. Delta 27A M-MuLV induced disease with a longer latency than did M-MuLV (7 versus 3 months) in greater than 85% of inoculated mice. More interestingly, this virus showed an expanded repertoire of hematopoietic diseases. Molecular analyses and histopathologic examinations indicated that while 39% of mice inoculated with Delta 27A M-MuLV developed T-cell lymphoblastic lymphoma typical of wild-type M-MuLV, the majority developed acute myeloid leukemia, erythroleukemia, or B-cell lymphoma. Viral DNA corresponding to Delta 27A M-MuLV was detectable in most of the tumors analyzed. These findings indicate that the GC-rich region significantly influences the disease specificity and latency of M-MuLV.
Hanecak
R
R
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717.
Pattengale
P K
PK
Fan
H
H
D000818:Animals; D000831:Animals, Newborn; D001482:Base Composition; D001483:Base Sequence; D002872:Chromosome Deletion; D003596:Cytosine; D004742:Enhancer Elements, Genetic; D005814:Genes, Viral; D006147:Guanine; D007942:Leukemia, Experimental / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics* / Q000472:pathogenicity; D015345:Oligonucleotide Probes; D011289:Preleukemia / Q000382:microbiology* / Q000473:pathology; D012091:Repetitive Sequences, Nucleic Acid
D015345:Oligonucleotide Probes; D006147:Guanine; D003596:Cytosine