Virulence in lymphomagenesis is modulated by alterations in proteins binding to CORE and GRE-LVa elements of the MoMuLV enhancer.
Changing nucleotide 3 of the CORE consensus from T to C has no effect on the binding of a 42 kDa protein, which has little affinity for the CCAAT binding site. Changing nucleotide 6 of the CORE consensus from T to C significantly reduces binding of the 42 kDa protein. Studies on the pathology induced by various MoMuLV mutants with CORE mutations showed that the CORE elements are important in modulating virulence in T-cell lymphomagenesis in BALB/c mice. However, disease specificity appears to be influenced as much by the host as it is by the virus. LVa is preferentially bound to the GRE-LVa sites. Deletion of nucleotide 9 and changing nucleotides 10 and 11 from GG to AA in the GRE-LVa element does not disrupt binding of LVa. Changing nucleotide 10 from G to A and nucleotide 13 from A to T in the GRE-LVa element does not disrupt binding of GR but allows binding of a novel protein which displaces or abolishes binding of LVa. These five nucleotide changes alone do not alter disease specificity and had a minimal effect on virulence in T-cell lymphomagenesis in BALB/c mice. Additionally, changing nucleotide 3 in CORE(a) and nucleotide 6 in CORE(b) does not alter disease specificity but has a small additional effect on virulence in T-cell lymphomagenesis.
Yuen
P H
PH
University of Texas System Cancer Center, Science Park-Research Division, Smithville 78957.
Khang
Y H
YH
Matherne
C
C
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000209:etiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000472:pathogenicity*; D009154:Mutation; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014774:Virulence / Q000235:genetics
D014758:Viral Core Proteins; D014764:Viral Proteins