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Moloney murine leukemia virus long terminal repeat activates monocyte chemotactic protein‐1 protein expression and chemotactic activity
Author(s) -
Faller Douglas V.,
Weng Haiqin,
Graves Dana T.,
Choi SangYun
Publication year - 1997
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199708)172:2<240::aid-jcp11>3.0.co;2-d
Subject(s) - long terminal repeat , microbiology and biotechnology , hela , chemotaxis , monocyte , biology , chemokine , retrovirus , murine leukemia virus , jurkat cells , gene , polyclonal antibodies , virus , cell culture , gene expression , virology , antibody , t cell , immunology , inflammation , immune system , receptor , biochemistry , genetics
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. J. Cell. Physiol. 172:240–252, 1997. © 1997 Wiley‐Liss, Inc.