Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses.

Chatis, Pamela A.; Holland, Christie A.; Hartley, Janet W.; Rowe, Wallace P.; Hopkins, Nancy

doi:10.1073/pnas.80.14.4408

Cited by 223 publications

(150 citation statements)

References 23 publications

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“…It has long been speculated that the ability of Moloney MLV to cause lymphomas is due to the successful replication of the virus in lymphoid tissue (Jaenisch 1979;Chatis et al 1983;Evans and Morrey 1987;Speck et al 1990). The ability of the retroviral LTR to exploit a lymphoid transcription factor would explain in part this success.…”

Section: ~Fllelltdks-cqsfis~tg-dgwe-fklsdpde~arr~skrknkpkmnyeklsrglrymentioning

confidence: 99%

Sequence-specific DNA binding of the proto-oncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the Moloney murine sarcoma virus.

Gunther¹,

Nye²,

Bryner³

et al. 1990

Genes Dev.

177

101

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The ets proto-oncogene family is a group of sequence-related genes whose normal cellular function is unknown. In a study of cellular proteins involved in the transcriptional regulation of murine retroviruses in T lymphocytes, we have discovered that a member of the ets gene family encodes a sequence-specific DNAbinding protein. A mouse ets-1 cDNA clone was obtained by screening a mouse thymus cDNA expression library with a double-stranded oligonucleotide probe representing 20 bp of the Moloney murine sarcoma virus (MSV) long terminal repeat (LTR). The cDNA sequence has an 813-bp open reading frame (ORF) whose predicted amino acid sequence is 97.6% identical to the 272 carboxy-terminal amino acids of the human ets-1 protein. The ORF was expressed in bacteria, and the 30-kD protein product was shown to bind DNA in a sequence-specific manner by mobility-shift assays, Southwestern blot analysis, and methylation interference. A mutant LTR containing four base pair substitutions in the ets-1 binding site was constructed and was shown to have reduced binding in vitro. Transcriptional efficiency of the MSV LTR promoter containing this disrupted ets-1 binding site was compared to the activity of a wild-type promoter in mouse T lymphocytes in culture, and 15-to 20-fold reduction in expression of a reporter gene was observed. We propose that ets-1 functions as a transcriptional activator of mammalian type-C retroviruses and speculate that ets-related genes constitute a new group of eukaryotic DNA-binding proteins.

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Section: ~Fllelltdks-cqsfis~tg-dgwe-fklsdpde~arr~skrknkpkmnyeklsrglrymentioning

confidence: 99%

Sequence-specific DNA binding of the proto-oncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the Moloney murine sarcoma virus.

Gunther¹,

Nye²,

Bryner³

et al. 1990

Genes Dev.

177

101

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“…This recombinant will grow as an infectious though less efficient virus on 3T6 cells following DNA transfection (23). As the lymphotropism of Mo-MuLV is known to be associated with its LTR sequence (24), it was rationalized that the enhancer region within this LTR may function as a lymphotropic element. However, it was found that this recombinant virus had a tissue specificity for replication in the pancreas.…”

mentioning

confidence: 99%

A pancreas specificity results from the combination of polyomavirus and Moloney murine leukemia virus enhancer.

Rochford¹,

Campbell²,

Villarreal³

1987

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

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“…Moloney MuLV induces T-cell lymphomas, whereas Friend MuLV induces erythroleukemia when injected into newborn mice (54,65). Using recombinant viruses, disease tropism was mapped to the viral LTR (5,6). Further studies demonstrated that specific enhancer sequences within the Moloney MuLV LTR in cooperation with unique T-cell transcription factors were the primary determinants for the distinct cell tropism (3,42).…”

Section: Discussionmentioning

confidence: 99%

Envelope Is a Major Viral Determinant of the Distinct In Vitro Cellular Transformation Tropism of Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2

Xie¹,

Green

2005

J Virol

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Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are related deltaretroviruses but are distinct in their disease-inducing capacity. These viruses can infect a variety of cell types, but only T lymphocytes become transformed, which is defined in vitro as showing indefinite interleukin-2-independent growth. Studies have indicated that HTLV-1 has a preferential tropism for CD4 ؉ T cells in vivo and is associated with the development of leukemia and neurological disease. Conversely, the in vivo T-cell tropism of HTLV-2 is less clear, although it appears that CD8 ؉ T cells preferentially harbor the provirus, with only a few cases of disease association. The difference in T-cell transformation tropism has been confirmed in vitro as shown by the preferential transformation of CD4 ؉ T cells by HTLV-1 versus the transformation of CD8 ؉ T cells by HTLV-2. Our previous studies showed that Tax and overlapping Rex do not confer the distinct T-cell transformation tropisms between HTLV-1 and HTLV-2. Therefore, for this study HTLV-1 and HTLV-2 recombinants were generated to assess the contribution of LTR and env sequences in T-cell transformation tropism. Both sets of proviral recombinants expressed p19 Gag following transfection into cells. Furthermore, recombinant viruses were replication competent and had the capacity to transform T lymphocytes. Our data showed that exchange of the env gene resulted in altered T-cell transformation tropism compared to wild-type virus, while exchange of long terminal repeat sequences had no significant effect. HTLV-2/Env1 preferentially transformed CD4 ؉ T cells similarly to wild-type HTLV-1 (wtHTLV-1), whereas HTLV-1/Env2 had a transformation tropism similar to that of wtHTLV-2 (CD8 ؉ T cells). These results indicate that env is a major viral determinant for HTLV T-cell transformation tropism in vitro and provides strong evidence implicating its contribution to the distinct pathogenesis resulting from HTLV-1 versus HTLV-2 infections.

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Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses.

Cited by 223 publications

References 23 publications

Sequence-specific DNA binding of the proto-oncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the Moloney murine sarcoma virus.

Sequence-specific DNA binding of the proto-oncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the Moloney murine sarcoma virus.

A pancreas specificity results from the combination of polyomavirus and Moloney murine leukemia virus enhancer.

Envelope Is a Major Viral Determinant of the Distinct In Vitro Cellular Transformation Tropism of Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2

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