Moloney murine leukemia virus long terminal repeat activates monocyte chemotactic protein-1 protein expression and chemotactic activity

Douglas V. Faller, Haiqin Weng, Dana T. Graves, Sang-Yun Choi

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Moloney murine leukemia virus (Mo-MuLV) is a thymotropic and leukemogenic retrovirus which causes T lymphomas. Recently, Mo-MuLV has been shown to trans-activate cellular genes. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine which can promote the migration and diapedesis of monocytes and lymphocytes, as well as inducing metastasis of lymphomas. Here we demonstrate that introduction of Mo-MuLV or the MuLV LTR alone, transiently or stably, into Balb/c-3T3 cells or HeLa cells resulted in 9-11 fold increases in MCP-1 transcripts. This trans-activation of the MCP-1 gene by the Mo-MuLV LTR is independent of the physical location of the MCP-1 gene or of the LTR, occurring whether the LTR or the MCP-1 gene is integrated in the genome or transiently expressed. Immunoblot analysis using an anti-MCP-1 polyclonal antibody showed that the expression of the MuLV LTR in HeLa cells also induced the appearance of the MCP-1 protein. Boyden Chamber analysis demonstrated that the MCP-1 chemotactic activity produced by HeLa cells with an integrated MuLV LTR was elevated by 11 fold and that neutralizing antibody to human MCP-1 abrogated monocyte migration in response to MuLV LTR expression. Promoter deletional analysis showed the LTR responsive cis-acting element in the MCP-1 promoter is located between -141 and -88. Deletion of this region abolished the trans-activation of MCP-1 by the LTR. These LTR-mediated activations of a chemotactic and inflammatory cytokine may be relevant as mechanisms whereby retroviruses which do not contain oncogenes can induce neoplasia.

Original languageEnglish
Pages (from-to)240-252
Number of pages13
JournalJournal of Cellular Physiology
Volume172
Issue number2
DOIs
Publication statusPublished - 1997 Aug 1
Externally publishedYes

Fingerprint

Moloney murine leukemia virus
Terminal Repeat Sequences
Chemokine CCL2
Viruses
Proteins
Genes
HeLa Cells
Chemical activation
Retroviridae
Chemokines
Monocytes
Lymphoma
Transendothelial and Transepithelial Migration
3T3 Cells
Lymphocytes
Neutralizing Antibodies
Oncogenes
Genome
Cytokines
Neoplasm Metastasis

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Moloney murine leukemia virus long terminal repeat activates monocyte chemotactic protein-1 protein expression and chemotactic activity. / Faller, Douglas V.; Weng, Haiqin; Graves, Dana T.; Choi, Sang-Yun.

In: Journal of Cellular Physiology, Vol. 172, No. 2, 01.08.1997, p. 240-252.

Research output: Contribution to journalArticle

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