To investigate the role of proviral integration and expression in cellular transformation induced by bovine leukemia virus (BLV), three BLV-induced tumors harboring a single proviral copy were selected upon restriction and hybridization analysis. Tumors 344 and 395 were shown to contain a full-size proviral copy, whereas in tumor 1345 the provirus appeared to be heavily deleted. RNA gel blot hy...

Retroelements constitute a large part of the human genome. These sequences are mostly silenced in normal cells, but genome-wide DNA hypomethylation in cancers might lead to their re-expression. Whether this re-expression really occurs in human cancers is largely unkown. We therefore investigated expression and DNA methylation of several classes of retroelements in human prostate cancer tissues ...

The MMTVD/myc transgenic mice spontaneously develop oligoclonal CD4+CD8+ T-cell tumors. We used provirus insertional mutagenesis in these mice to identify putative collaborators of c-myc. We found that Notch1 was mutated in a high proportion (52%) of these tumors. Proviruses were inserted upstream of the exon coding for the transmembrane domain and in both transcriptional orientations. These mu...

The repetitive ETn (early transposon) family of sequences represents an active "mobile mutagen" in the mouse genome. The presence of long terminal repeats (LTRs) and other diagnostic features indicate that ETns are retrotransposons but they contain no long open reading frames or documented similarity to the genes of known retroviruses or other retroelements. Thus, the mechanisms responsible for...

Retroviruses that have the ability to infect germ line cells can become an integral and inherited part of the host genome. About 8% of the human chromosomal DNA consists of sequences derived from infections by retroviruses that presumably circulated 2-40 millions of years ago, and some elements are actually much older. Post-insertional recombinations, deletions, and mutations have rendered all ...

The major obstacle to curing HIV infection is the persistence of cells with intact proviruses that can produce replication-competent virus. This HIV reservoir is believed to exist primarily in CD4+ T-cells and is stable despite years of suppressive antiretroviral therapy. A potential mechanism for HIV persistence is clonal expansion of infected cells, but how often such clones carry replication...

We have molecularly cloned a feline leukemia virus (FeLV) (clone 33) from a domestic cat with acute myeloid leukemia (AML). The long terminal repeat (LTR) of this virus, like the LTRs present in FeLV proviruses from other cats with AML, contains an unusual structure in its U3 region upstream of the enhancer (URE) consisting of three tandem direct repeats of 47 bp. To test the disease potential ...

Results of transient-expression studies have suggested a correlation between tissue-specific pathogenicity of murine leukemia viruses and the relative transcriptional activities of their long terminal repeats in various cell types. To test whether transient-expression ratios are representative of those of integrated proviruses, we developed a system for generation of retroviral transmission vec...

In a previous study we have shown that a single infectious particle of Moloney murine leukaemia virus per cell is sufficient to facilitate chemical carcinogenesis in normal rat kidney cells. When these cells are exposed to the carcinogen after a low number of passages post-infection (p.i.), cell transformation becomes apparent only after many subsequent passages. On the other hand, when exposur...

We determined the phenotype and genotype of murine leukemia viruses associated with the development of spontaneous nonthymic lymphomas in the high-leukemia mouse strain CWD/J. By T1 oligonucleotide fingerprint analysis of the viral RNA, the ecotropic viruses recovered from the spleen or thymus of preleukemic CWD/J mice were found to represent the progeny of the two endogenous ecotropic provirus...