Leukemogenicity of moloney murine leukemia viruses carrying polyoma enhancer sequences in the long terminal repeat is dependent on the nature of the inserted polyoma sequences

Fan, Hung; Chute, Hilary; Chao, Euphemia; Pattengale, Paul K.

doi:10.1016/0042-6822(88)90146-8

Cited by 20 publications

(31 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Those variants that efficiently generated MCF recombinants were the most pathogenic, while those that could not were the least. With regard to the polyoma-containing variants, we previously showed that the exact organization of the PyF101 enhancers are important for the low leukemogenicity in that chimeric Mo-MuLV LTRs with related F441 and wild-type polyoma enhancers were not as tightly restricted for disease (14). These viruses showed intermediate levels of MCF recombinant generation, consistent with their pathogenicity.…”

Section: Discussionmentioning

confidence: 75%

An enhancer variant of Moloney murine leukemia virus defective in leukemogenesis does not generate detectable mink cell focus-inducing virus in vivo.

Brightman

Rein

Trepp

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Moloney murine leukemia virus (Mo-MuLV) induces T-cell lymphoma when inoculated into neonatal mice. This is a multistep process. Early events observed in infected mice include generalized hematopoietic hyperplasia in the spleen and appearance of mink cell focus-inducing (MCF) recombinants; end-stage tumors are characterized by insertional proviral activation of protooncogenes. We previously showed that an Mo-MuLV enhancer variant, Mo+PyF101Mo-MuLV, has greatly reduced leukemogenicity and is deficient in induction of preleukemic hyperplasia. In this report, we have examined Mo+PyF101 Mo-MuLV-inoculated mice for the presence of MCF recombinants. In contrast to wild-type Mo-MuLV-inoculated mice, Mo+PyF101 Mo-MuLV-inoculated mice did not generate detectable MCF recombinants. This failure was at least partly due to an inability of the MCF virus to propagate in vivo, since a molecularly cloned infectious Mo+PyF101 MCF virus did not replicate, even when inoculated as a Mo+PyF101 Mo-MuLV pseudotype. These results show that the leukemogenic defect of Mo+PyF101 Mo-MuLV is associated with its inability to generate MCF recombinants capable of replication in vivo. This, in turn, is consistent with the view that MCF recombinants play a significant role in Mo-MuLV-induced disease and, in particular, may play a role early in the disease process.

show abstract

Section: Discussionmentioning

confidence: 75%

An enhancer variant of Moloney murine leukemia virus defective in leukemogenesis does not generate detectable mink cell focus-inducing virus in vivo.

Brightman

Rein

Trepp

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…MoMLV thus served as the helper virus in packaging pLaxlSN transcripts. The generation of replication competent retroviruses in the CM of these transduced 3T3 cells was con®rmed by the presence of reverse transcriptase activity as previously described (data not shown) (Fan et al, 1988).…”

Section: Generation Of Transforming Axl Mutantsmentioning

confidence: 99%

Determinants for transformation induced by the Axl receptor tyrosine kinase

et al. 1998

View full text Add to dashboard Cite

The Axl receptor tyrosine kinase is a transforming oncogene in NIH3T3 cells. In order to de®ne structural requirements of the Axl receptor necessary for transformation we passaged recombinant retroviruses carrying the axl cDNA in NIH3T3 cells, generating randomly mutated axl variants. Using this strategy, we have isolated three axl viral strains (1B1, SV8, and FFa4) that show augmented 3T3 cell transforming capacity associated with elevated p140 Axl . Upon sequencing, the 1B1 and SV8 proviruses possessed only silent mutations, making p140 Axl overexpression the most likely explanation for their increased transformation activity. However, the characterization of FFa4 revealed a deletion of sequences encoding the carboxy-terminal 45 amino acids leading to the generation of a chimeric transcript comprised of a truncated Axl receptor with a segment of the 3' UTR region. Mutational analysis revealed that the transforming activity of FFa4 was speci®c to the formation of the chimeric receptor rather than to the carboxyl-terminal truncation. Intriguingly, none of the viral strains were able to transform the murine cell lines NR-6 and 32D despite equivalent expression of surface p140 Axl protein. Further analysis showed that Axl's transforming potential is dependent on the host cell type, the presence of a putative pp190 as a facilitator for transformation, and the level of p140 Axl expression. Taken together, these results underscore the complexity of Axl biology which is dependent on receptor stoichiometry and the cellular background.

show abstract

“…Southern blot analysis was used to detect clonal MoFe2 insertions at loci commonly targeted for integration in tumors induced by either M-MuLV or FeLV-945. Previous studies have shown that cmyc, pvt-1, and pim-1 and are targets of M-MuLV integration in ϳ50, ϳ10, and ϳ60% of lymphomas examined, respectively (10,14,47). FeLV-945 was not found to integrate at any of these loci but was identified at a locus termed flvi-1 in 36% of tumors examined (1,24).…”

Section: And Cd4mentioning

confidence: 99%

“…Specifically, LTRs in relatively early appearing tumors (19 to 23 weeks) retained the original MoFe2 LTR intact and unaltered, but LTRs in late-appearing tumors (29 to 41 weeks) had acquired various duplications of the enhancer (43). In the present study, the sequences of LTRs were examined from five insertions at MF8T and from three insertions at [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. This analysis demonstrated that all LTRs retained the original sequence intact and unaltered (data not shown).…”

Section: And Cd4mentioning

confidence: 99%

Substitution of Feline Leukemia Virus Long Terminal Repeat Sequences into Murine Leukemia Virus Alters the Pattern of Insertional Activation and Identifies New Common Insertion Sites

Johnson

Lobelle‐Rich²,

Puetter

et al. 2005

J Virol

View full text Add to dashboard Cite

Leukemogenicity of moloney murine leukemia viruses carrying polyoma enhancer sequences in the long terminal repeat is dependent on the nature of the inserted polyoma sequences

Cited by 20 publications

References 28 publications

An enhancer variant of Moloney murine leukemia virus defective in leukemogenesis does not generate detectable mink cell focus-inducing virus in vivo.

An enhancer variant of Moloney murine leukemia virus defective in leukemogenesis does not generate detectable mink cell focus-inducing virus in vivo.

Determinants for transformation induced by the Axl receptor tyrosine kinase

Substitution of Feline Leukemia Virus Long Terminal Repeat Sequences into Murine Leukemia Virus Alters the Pattern of Insertional Activation and Identifies New Common Insertion Sites

Contact Info

Product

Resources

About