当前位置： SCI文献检索 > JOURNAL OF VIROLOGY期刊下所有文献 > Selection of reversions and suppressors of a mutation in the CBF binding site of a lymphomagenic retrovirus.

Selection of reversions and suppressors of a mutation in the CBF binding site of a lymphomagenic retrovirus.

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-pair substitution in each of the two core elements. This mutation significantly attenuates 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 might account for the predominance of the reversions and suppressor mutations in tumor 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 a consequence 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 three or 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 repeats endowed the cells containing them with a selective growth advantage.

journal_name

J Virol

journal_title

Journal of virology

authors

Martiney MJ,Rulli K,Beaty R,Levy LS,Lenz J

doi

10.1128/JVI.73.9.7599-7606.1999

subject

Has Abstract

pub_date

1999-09-01 00:00:00

pages

7599-606

issue

eissn

0022-538X

issn

1098-5514

journal_volume

pub_type

杂志文章

在线工具

Selection of reversions and suppressors of a mutation in the CBF binding site of a lymphomagenic retrovirus.