Hypoxia inhibits Moloney murine leukemia virus expression in activated macrophages

Maura Puppo, Maria Carla Bosco, Maurizio Federico, Sandra Pastorino, Luigi Varesio

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Hypoxia, a local decrease in oxygen tension, occurring in many pathological processes, modifies macrophage (Mφ) gene expression and function. Here, we provide the first evidence that hypoxia inhibits transgene expression driven by the Moloney murine leukemia virus-long terminal repeats (MoMLV-LTR) in IFN-γ-activated Mφ. Hypoxia silenced the expression of several MoMLV-LTR-driven genes, including v-myc, enhanced green fluorescence protein, and env, and was effective in different mouse Mφ cell lines and on distinct MoMLV backbone-based viruses. Down-regulation of MoMLV mRNA occurred at the transcriptional level and was associated with decreased retrovirus production, as determined by titration experiments, suggesting that hypoxia may control MoMLV retroviral spread through the suppression of LTR activity. In contrast, genes driven by the CMV or the SV40 promoter were up-regulated or unchanged by hypoxia, indicating a selective inhibitory activity on the MoMLV promoter. It is interesting that hypoxia was ineffective in suppressing MoMLV-LTR-controlled gene expression in T or fibroblast cell lines, suggesting a Mφ lineage-selective action. Finally, we found that MoMLV-mediated gene expression in Mφ was also inhibited by picolinic acid, a tryptophan catabolite with hypoxia-like activity and Mφ-activating properties, suggesting a pathophysiological role of this molecule in viral resistance and its possible use as an antiviral agent.

Original languageEnglish
Pages (from-to)528-538
Number of pages11
JournalJournal of Leukocyte Biology
Volume81
Issue number2
DOIs
Publication statusPublished - Feb 1 2007

Fingerprint

Moloney murine leukemia virus
Macrophages
Terminal Repeat Sequences
Gene Expression
env Gene Products
Cell Line
myc Genes
Pathologic Processes
Retroviridae
Hypoxia
Transgenes
Tryptophan
Antiviral Agents
Down-Regulation
Fibroblasts
Fluorescence
Oxygen
Viruses
Messenger RNA

Keywords

  • Gene regulation
  • Monocytes
  • Retrovirus

ASJC Scopus subject areas

  • Cell Biology

Cite this

Hypoxia inhibits Moloney murine leukemia virus expression in activated macrophages. / Puppo, Maura; Bosco, Maria Carla; Federico, Maurizio; Pastorino, Sandra; Varesio, Luigi.

In: Journal of Leukocyte Biology, Vol. 81, No. 2, 01.02.2007, p. 528-538.

Research output: Contribution to journalArticle

Puppo, Maura ; Bosco, Maria Carla ; Federico, Maurizio ; Pastorino, Sandra ; Varesio, Luigi. / Hypoxia inhibits Moloney murine leukemia virus expression in activated macrophages. In: Journal of Leukocyte Biology. 2007 ; Vol. 81, No. 2. pp. 528-538.
@article{fdd4636e786245149443ccc620295844,
title = "Hypoxia inhibits Moloney murine leukemia virus expression in activated macrophages",
abstract = "Hypoxia, a local decrease in oxygen tension, occurring in many pathological processes, modifies macrophage (Mφ) gene expression and function. Here, we provide the first evidence that hypoxia inhibits transgene expression driven by the Moloney murine leukemia virus-long terminal repeats (MoMLV-LTR) in IFN-γ-activated Mφ. Hypoxia silenced the expression of several MoMLV-LTR-driven genes, including v-myc, enhanced green fluorescence protein, and env, and was effective in different mouse Mφ cell lines and on distinct MoMLV backbone-based viruses. Down-regulation of MoMLV mRNA occurred at the transcriptional level and was associated with decreased retrovirus production, as determined by titration experiments, suggesting that hypoxia may control MoMLV retroviral spread through the suppression of LTR activity. In contrast, genes driven by the CMV or the SV40 promoter were up-regulated or unchanged by hypoxia, indicating a selective inhibitory activity on the MoMLV promoter. It is interesting that hypoxia was ineffective in suppressing MoMLV-LTR-controlled gene expression in T or fibroblast cell lines, suggesting a Mφ lineage-selective action. Finally, we found that MoMLV-mediated gene expression in Mφ was also inhibited by picolinic acid, a tryptophan catabolite with hypoxia-like activity and Mφ-activating properties, suggesting a pathophysiological role of this molecule in viral resistance and its possible use as an antiviral agent.",
keywords = "Gene regulation, Monocytes, Retrovirus",
author = "Maura Puppo and Bosco, {Maria Carla} and Maurizio Federico and Sandra Pastorino and Luigi Varesio",
year = "2007",
month = "2",
day = "1",
doi = "10.1189/jlb.0506361",
language = "English",
volume = "81",
pages = "528--538",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "FASEB",
number = "2",

}

TY - JOUR

T1 - Hypoxia inhibits Moloney murine leukemia virus expression in activated macrophages

AU - Puppo, Maura

AU - Bosco, Maria Carla

AU - Federico, Maurizio

AU - Pastorino, Sandra

AU - Varesio, Luigi

PY - 2007/2/1

Y1 - 2007/2/1

N2 - Hypoxia, a local decrease in oxygen tension, occurring in many pathological processes, modifies macrophage (Mφ) gene expression and function. Here, we provide the first evidence that hypoxia inhibits transgene expression driven by the Moloney murine leukemia virus-long terminal repeats (MoMLV-LTR) in IFN-γ-activated Mφ. Hypoxia silenced the expression of several MoMLV-LTR-driven genes, including v-myc, enhanced green fluorescence protein, and env, and was effective in different mouse Mφ cell lines and on distinct MoMLV backbone-based viruses. Down-regulation of MoMLV mRNA occurred at the transcriptional level and was associated with decreased retrovirus production, as determined by titration experiments, suggesting that hypoxia may control MoMLV retroviral spread through the suppression of LTR activity. In contrast, genes driven by the CMV or the SV40 promoter were up-regulated or unchanged by hypoxia, indicating a selective inhibitory activity on the MoMLV promoter. It is interesting that hypoxia was ineffective in suppressing MoMLV-LTR-controlled gene expression in T or fibroblast cell lines, suggesting a Mφ lineage-selective action. Finally, we found that MoMLV-mediated gene expression in Mφ was also inhibited by picolinic acid, a tryptophan catabolite with hypoxia-like activity and Mφ-activating properties, suggesting a pathophysiological role of this molecule in viral resistance and its possible use as an antiviral agent.

AB - Hypoxia, a local decrease in oxygen tension, occurring in many pathological processes, modifies macrophage (Mφ) gene expression and function. Here, we provide the first evidence that hypoxia inhibits transgene expression driven by the Moloney murine leukemia virus-long terminal repeats (MoMLV-LTR) in IFN-γ-activated Mφ. Hypoxia silenced the expression of several MoMLV-LTR-driven genes, including v-myc, enhanced green fluorescence protein, and env, and was effective in different mouse Mφ cell lines and on distinct MoMLV backbone-based viruses. Down-regulation of MoMLV mRNA occurred at the transcriptional level and was associated with decreased retrovirus production, as determined by titration experiments, suggesting that hypoxia may control MoMLV retroviral spread through the suppression of LTR activity. In contrast, genes driven by the CMV or the SV40 promoter were up-regulated or unchanged by hypoxia, indicating a selective inhibitory activity on the MoMLV promoter. It is interesting that hypoxia was ineffective in suppressing MoMLV-LTR-controlled gene expression in T or fibroblast cell lines, suggesting a Mφ lineage-selective action. Finally, we found that MoMLV-mediated gene expression in Mφ was also inhibited by picolinic acid, a tryptophan catabolite with hypoxia-like activity and Mφ-activating properties, suggesting a pathophysiological role of this molecule in viral resistance and its possible use as an antiviral agent.

KW - Gene regulation

KW - Monocytes

KW - Retrovirus

UR - http://www.scopus.com/inward/record.url?scp=33846670516&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846670516&partnerID=8YFLogxK

U2 - 10.1189/jlb.0506361

DO - 10.1189/jlb.0506361

M3 - Article

C2 - 17062606

AN - SCOPUS:33846670516

VL - 81

SP - 528

EP - 538

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 2

ER -