Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1999 Jun;73(6):4890-8.
doi: 10.1128/JVI.73.6.4890-4898.1999.

Sequences between the enhancer and promoter in the long terminal repeat affect murine leukemia virus pathogenicity and replication in the thymus

F K Yoshimura  1 , T Wang, M Cankovic
Affiliations

Sequences between the enhancer and promoter in the long terminal repeat affect murine leukemia virus pathogenicity and replication in the thymus

F K Yoshimura et al. J Virol. 1999 Jun.

Abstract

We previously showed that the 93-bp region between the enhancer and promoter (named DEN for downstream of enhancer) of the long terminal repeat (LTR) of the MCF13 murine leukemia virus is an important determinant of the ability of this virus to induce thymic lymphoma. In this study we observed that DEN plays a role in the regulation of virus replication in the thymus during the preleukemic period. A NF-kappaB site in the DEN region partially contributes to the effect of DEN on both lymphomagenicity and virus replication. To further study the effects of DEN and the NF-kappaB site on viral pathogenicity during the preleukemic period, we examined replication of wild-type and mutant viruses with a deletion of the NF-kappaB site or the entire DEN region in the thymus. Thymic lymphocytes which were infected with wild-type and mutant viruses were predominantly the CD3(-) CD4(+) CD8(+) and CD3(+) CD4(+) CD8(+) cells. The increase in infection by wild-type virus and both mutant viruses of these two subpopulations during the preleukemic period ranged from 9- to 84-fold, depending upon the time point and virus. The major difference between the wild-type and both mutant viruses was the lower rate and lower level of mutant virus replication in these thymic subpopulations. Significant differences in replication between wild-type and both mutant viruses were seen in the CD3(-) CD4(+) CD8(+) and CD3(-) CD4(-) CD8(-) subpopulations, suggesting that these thymic cell types are important targets for viral transformation.

PubMed Disclaimer

Figures

FIG. 1
FIG. 1
LTR of the MCF13 MLV. The CAT and TATA boxes of the basal promoter are indicated. Upstream regulatory sequences consisting of the tandemly repeated 69-bp enhancer and 93-bp DEN region are also shown. The sequence of the NF-κB site within DEN is indicated. Numbering is relative to the start site of transcription, which is marked by the horizontal arrow.
FIG. 2
FIG. 2
Thymic lymphoma incidence for WT, ΔNF-κB, and ΔDEN MCF13 viruses. Neonatal AKR/J mice were inoculated intraperitoneally with 1 × 106 to 2.5 × 106 infectious units of each virus. The time course of appearance of thymic lymphoma is shown. Symbols: □, WT; ○, ΔNF-κB; ◊, ΔDEN.
FIG. 3
FIG. 3
Thymic lymphocytes expressing MCF13 envelope gp70. Lymphocytes were isolated from thymuses removed from mice after virus inoculation at 3, 4, 6, and 8 weeks. A total of 106 lymphocytes were stained with the primary MAb 514, followed with the secondary FITC-conjugated goat anti-mouse IgG. A total of 2 × 104 lymphocytes were analyzed by flow cytometry, and the percentage of gp70+ lymphocytes was calculated with the Paint-a-Gate software (BDIS). Percentages of gp70+ cells for individual mice are shown. Mean values are connected by a solid line. Control (A), WT (B), ΔNF-κB (C), and ΔDEN MCF13 (D) virus were used.
FIG. 4
FIG. 4
Infectious center assays of thymic lymphocytes. Lymphocytes were isolated from thymuses removed from mice after virus inoculation at 3, 4, 6, and 8 weeks. A total of 1 × 102 to 5 × 103 lymphocytes were plated onto M. dunni fibroblasts. The cell cultures were allowed to grow to confluency. Cells were stained with MAb 514 and FITC-conjugated goat anti-mouse IgG. Infectious center assay data are represented as percentages of the numbers of plated thymic lymphocytes. Each point corresponds to an individual mouse. Mean values are connected by a solid line. Control (A), WT (B), ΔNF-κB (C), and ΔDEN MCF13 (D) virus were used.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Arima N, Molitor J A, Smith M R, Kim J H, Daitoku Y, Greene W C. Human T-cell leukemia virus type I Tax induces expression of the Rel-related family of κB enhancer-binding proteins: evidence for a pretranslational component of regulation. J Virol. 1991;65:6892–6899. - PMC - PubMed
    1. Baeuerle P A, Henkel T. Function and activation of NF-κB in the immune system. Annu Rev Immunol. 1994;12:141–179. - PubMed
    1. Barnes P J, Karin M. Nuclear factor-κB—a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336:1066–1071. - PubMed
    1. Boral S L, Okenquist A, Lenz J. Identification of the SL3-3 virus enhancer core as a T-lymphoma cell-specific element. J Virol. 1989;63:76–84. - PMC - PubMed
    1. Bowers W J, Baglia L A, Ruddell A. Regulation of avian leukosis virus long terminal repeat-enhanced transcription by C/EBP-Rel interactions. J Virol. 1996;70:3051–3059. - PMC - PubMed

Publication types