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Titolo:
Selection of reversions and suppressors of a mutation in the CBF binding site of a lymphomagenic retrovirus
Autore:
Martiney, MJ; Rulli, K; Beaty, R; Levy, LS; Lenz, J;
Indirizzi:
Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA Albert Einstein Coll Med Bronx NY USA 10461 ol Genet, Bronx, NY 10461 USA Tulane Univ, Sch Med, New Orleans, LA 70112 USA Tulane Univ New Orleans LA USA 70112 , Sch Med, New Orleans, LA 70112 USA
Titolo Testata:
JOURNAL OF VIROLOGY
fascicolo: 9, volume: 73, anno: 1999,
pagine: 7599 - 7606
SICI:
0022-538X(199909)73:9<7599:SORASO>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
MURINE LEUKEMIA-VIRUS; I TRANSCRIPTIONAL ACTIVATORS; DISEASE SPECIFICITY; ENHANCER VARIANT; T-LYMPHOCYTES; SL3-3; CORE; SEQUENCES; REPEAT; IDENTIFICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Lenz, J Albert Einstein Coll Med, Dept Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA Albert Einstein Coll Med 1300 Morris Pk Ave Bronx NY USA 10461 USA
Citazione:
M.J. Martiney et al., "Selection of reversions and suppressors of a mutation in the CBF binding site of a lymphomagenic retrovirus", J VIROLOGY, 73(9), 1999, pp. 7599-7606

Abstract

The retrovirus SL3 induces T-cell lymphomas in mice. The transcriptional enhancer in the long terminal repeat (LTR) of SL3 contains two 72-bp repeats. Each repeat contains a binding site for the transcription factor CBF (also called AML1). The CBF binding sites are called core elements. SAA is a mutant that is identical to SL3 except for the presence of a single-base-pairsubstitution in each of the two core elements. This mutation significantlyattenuates viral lymphomagenicity. Most lymphomas that occur in SAA-infected mice contain proviruses with reversions or second-site suppressor mutations within the core element. We examined the selective pressures that mightaccount for the predominance of the reversions and suppressor mutations intumor proviruses by analyzing when proviruses with altered core sequences became abundant during the course of lymphomagenesis. Altered core sequences were easily detected in thymus DNAs by 4 to 6 weeks after SAA infection of mice, well before lymphomas were grossly evident. This result is consistent with the hypothesis that viruses with the core sequence alterations emerged because they replicated more effectively in mice than SAA. The number of 72-bp tandem, repeats in the viral LTR was found to vary, presumably as aconsequence of reverse transcriptase slippage during polymerization. Proviruses with two repeats predominated in the thymuses of SAA- and SL3-infected mice before lymphomas developed, although LTRs with one or three repeats were also present. This suggested that two was the optimal number of 72-bp repeats for viral replication. However, in lymphomas, proviruses with threeor four repeats usually predominated. This suggested that a late step in the process of lymphomagenesis led to the abundance of proviruses with additional repeats. We hypothesize that proviruses with additional 72-bp repeatsendowed the cells containing them with a selective growth advantage.

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Documento generato il 15/01/21 alle ore 23:16:22