Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Virology |
| Vol/bind | 79 |
| Udgave nummer | 1 |
| Sider (fra-til) | 67-78 |
| Antal sider | 11 |
| ISSN | 0022-538X |
| DOI | |
| Status | Udgivet - 2005 |
| Udgivet eksternt | Ja |
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I: Journal of Virology, Bind 79, Nr. 1, 2005, s. 67-78.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
TY - JOUR
T1 - Analysis of wild-type and mutant SL3-3 murine leukemia virus insertions in the c-myc promoter during lymphomagenesis reveals target site hot spots, virus-dependent patterns, and frequent error-prone gap repair.
AU - Nielsen, Anne Ahlmann
AU - Sørensen, Annette Balle
AU - Schmidt, Jörg
AU - Pedersen, Finn Skou
PY - 2005
Y1 - 2005
N2 - The murine leukemia retrovirus SL3-3 induces lymphomas in the T-cell compartment of the hematopoetic system when it is injected into newborn mice of susceptible strains. Previously, our laboratory reported on a deletion mutant of SL3-3 that induces T-cell tumors faster than the wild-type virus (S. Ethelberg, A. B. Sorensen, J. Schmidt, A. Luz, and F. S. Pedersen, J. Virol. 71:9796-9799, 1997). PCR analyses of proviral integrations in the promoter region of the c-myc proto-oncogene in lymphomas induced by wild-type SL3-3 [SL3-3(wt)] and the enhancer deletion mutant displayed a difference in targeting frequency into this locus. We here report on patterns of proviral insertions into the c-myc promoter region from SL3-3(wt), the faster variant, as well as other enhancer variants from a total of approximately 250 tumors. The analysis reveals (i) several integration site hot spots in the c-myc promoter region, (ii) differences in integration patterns between SL3-3(wt) and enhancer deletion mutant viruses, (iii) a correlation between tumor latency and the number of proviral insertions into the c-myc promoter, and (iv) a [5'-(A/C/G)TA(C/G/T)-3'] integration site consensus sequence. Unexpectedly, about 12% of the sequenced insertions were associated with point mutations in the direct repeat flanking the provirus. Based on these results, we propose a model for error-prone gap repair of host-provirus junctions.
AB - The murine leukemia retrovirus SL3-3 induces lymphomas in the T-cell compartment of the hematopoetic system when it is injected into newborn mice of susceptible strains. Previously, our laboratory reported on a deletion mutant of SL3-3 that induces T-cell tumors faster than the wild-type virus (S. Ethelberg, A. B. Sorensen, J. Schmidt, A. Luz, and F. S. Pedersen, J. Virol. 71:9796-9799, 1997). PCR analyses of proviral integrations in the promoter region of the c-myc proto-oncogene in lymphomas induced by wild-type SL3-3 [SL3-3(wt)] and the enhancer deletion mutant displayed a difference in targeting frequency into this locus. We here report on patterns of proviral insertions into the c-myc promoter region from SL3-3(wt), the faster variant, as well as other enhancer variants from a total of approximately 250 tumors. The analysis reveals (i) several integration site hot spots in the c-myc promoter region, (ii) differences in integration patterns between SL3-3(wt) and enhancer deletion mutant viruses, (iii) a correlation between tumor latency and the number of proviral insertions into the c-myc promoter, and (iv) a [5'-(A/C/G)TA(C/G/T)-3'] integration site consensus sequence. Unexpectedly, about 12% of the sequenced insertions were associated with point mutations in the direct repeat flanking the provirus. Based on these results, we propose a model for error-prone gap repair of host-provirus junctions.
U2 - 10.1128/JVI.79.1.67-78.2005
DO - 10.1128/JVI.79.1.67-78.2005
M3 - Journal article
C2 - 15596802
SN - 0022-538X
VL - 79
SP - 67
EP - 78
JO - Journal of Virology
JF - Journal of Virology
IS - 1
ER -