A single mutation in one of the core elements of moloney murine leukemia virus reduced binding of a 42-kDa T lymphoma cell nuclear factor but did not affect lymphomagenesis

1990 ◽  
Vol 3 (2) ◽  
pp. 93-102 ◽  
Author(s):  
Roger S. Case ◽  
Yong-Ho Khang ◽  
Abhay Kumar ◽  
Pick-Hoong Yuen
Keyword(s):  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Lymphoma Cell ◽  
Moloney Murine Leukemia Virus ◽  
Single Mutation ◽  
Nuclear Factor ◽  
The Core ◽  
Core Elements ◽  
T Lymphoma ◽  
Murine Leukemia

scholarly journals Phosphorylated Serine Residues and an Arginine-Rich Domain of the Moloney Murine Leukemia Virus p12 Protein Are Required for Early Events of Viral Infection

2003 ◽  
Vol 77 (3) ◽  
pp. 1820-1829 ◽  
Author(s):  
Andrew Yueh ◽  
Stephen P. Goff
Keyword(s):  
Murine Leukemia Virus ◽  
Molecular Mechanisms ◽  
Virus Assembly ◽  
Leukemia Virus ◽  
Mutant Virus ◽  
Moloney Murine Leukemia Virus ◽  
Single Mutation ◽  
Gag Protein ◽  
Murine Leukemia

ABSTRACT Mutational analyses of the p12 Gag phosphoprotein of Moloney murine leukemia virus have demonstrated its participation in both virus assembly and the early stages of infection. The molecular mechanisms by which p12 functions in these events are still poorly understood. We performed studies to examine the significance of p12 phosphorylation in the viral life cycle. Alanine substitutions were introduced at the potential phosphorylation sites in p12, and the resulting mutants were tested for replication. Mutant viruses with changes at S61 and S78 were severely impaired, whereas the other mutant viruses were viable. S61 was shown to be required for normal levels of phosphorylation of p12 in vivo. These defective mutant viruses showed no apparent alteration to Gag protein processing or reduction in the yield of virions after transient transfection, but the mutants failed to form circular viral DNAs in acutely infected cells. Sequence analysis of revertant clones derived from S(61,65)A mutant virus revealed two classes: one group with a single mutation at a residue adjacent to S61 and another group with mutations introducing new positive charges surrounding S61. In vivo [32P]orthophosphate labeling indicated that the rescue of the S(61,65)A mutant virus did not result in a significant increase in the phosphorylation level of p12. Alanine substitutions of an arginine-rich stretch near S61 (at R-66, -68, -70, and -71) resulted in the same phenotype as the S(61,65)A mutant virus. The restored function of S(61,65)A mutant virus by second or third site mutations may result from a structural change or the addition of positively charged residues in the arginine-rich region.

scholarly journals Mutation of the core or adjacent LVb elements of the Moloney murine leukemia virus enhancer alters disease specificity.

1990 ◽  
Vol 4 (2) ◽  
pp. 233-242 ◽  
Author(s):  
N A Speck ◽  
B Renjifo ◽  
E Golemis ◽  
T N Fredrickson ◽  
J W Hartley ◽  
...  
Keyword(s):  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
The Core ◽  
Disease Specificity ◽  
Murine Leukemia

scholarly journals Core-Binding Factor Influences the Disease Specificity of Moloney Murine Leukemia Virus

1999 ◽  
Vol 73 (7) ◽  
pp. 5535-5547 ◽  
Author(s):  
Amy F. Lewis ◽  
Terryl Stacy ◽  
William R. Green ◽  
Lekidelu Taddesse-Heath ◽  
Janet W. Hartley ◽  
...  
Keyword(s):  
T Cell ◽  
Latent Period ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Cell Disease ◽  
The Core ◽  
Core Site ◽  
Disease Specificity ◽  
Murine Leukemia

ABSTRACT The core site in the Moloney murine leukemia virus (Moloney MLV) enhancer was previously shown to be an important determinant of the T-cell disease specificity of the virus. Mutation of the core site resulted in a significant shift in disease specificity of the Moloney virus from T-cell leukemia to erythroleukemia. We and others have since determined that a protein that binds the core site, one of the core-binding factors (CBF) is highly expressed in thymus and is essential for hematopoiesis. Here we test the hypothesis that CBF plays a critical role in mediating pathogenesis of Moloney MLV in vivo. We measured the affinity of CBF for most core sites found in MLV enhancers, introduced sites with different affinities for CBF into the Moloney MLV genome, and determined the effects of these sites on viral pathogenesis. We found a correlation between CBF affinity and the latent period of disease onset, in that Moloney MLVs with high-affinity CBF binding sites induced leukemia following a shorter latent period than viruses with lower-affinity sites. The T-cell disease specificity of Moloney MLV also appeared to correlate with the affinity of CBF for its binding site. The data support a role for CBF in determining the pathogenic properties of Moloney MLV.

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