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Journal of virology1994; 68(10); 6270-6279; doi: 10.1128/JVI.68.10.6270-6279.1994

Monocyte maturation controls expression of equine infectious anemia virus.

Abstract: In vivo, equine infectious anemia virus (EIAV) replicates in tissues rich in macrophages, and it is widely believed that the tissue macrophage is the principal, if not sole, cell within the host that replicates virus. No viral replication has been detected in circulating peripheral blood monocytes. However, proviral DNA can be detected in these cells, and monocytes may serve as a reservoir for the virus. In this study, an in vitro model was developed to clarify the role of monocyte maturation in regulating EIAV expression. Freshly isolated, nonadherent equine peripheral blood monocytes were infected with a macrophage-tropic strain of EIAV, and expression of EIAV was monitored in cells held as nonadherent monocytes and cells allowed to adhere and differentiate into macrophages. A 2- to 3-day delay in viral antigen expression was observed in the nonadherent cells. This restriction of viral expression in monocytes was supported by nuclear run-on studies demonstrating that on day 5 postinfection, the level of actively transcribed viral messages was 4.7-fold lower in monocyte cultures than in macrophage cultures. Electrophoretic mobility shift assays identified three regions of the U3 enhancer that interacted with nuclear extracts from normal equine macrophages. Each region contained the core binding motif of a family of transcription factors that includes the product of the proto-oncogene ets. Antibodies to the Ets family member PU.1 caused a supershifting of retarded bands in an electrophoretic mobility shift assay. Transfection studies of ets motif mutants demonstrated that the U3 ets sites were important in the regulation of EIAV transcription in macrophages. Interactions between the ets motif and nuclear extracts from freshly isolated, nonadherent monocytes, macrophages adherent for 1 or 2 days, or macrophages adherent for 5 days gave different patterns of retarded bands, although the binding specificities were similar with all three extracts. The different complexes formed by monocyte and macrophage nuclear extracts may explain the enhanced ability of mature macrophages to support EIAV expression.
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Publication Date: 1994-10-01 PubMed ID: 8083967PubMed Central: PMC237047DOI: 10.1128/JVI.68.10.6270-6279.1994Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article examines the influence of monocyte maturation on the expression of the equine infectious anemia virus (EIAV), revealing that mature macrophages have a greater ability to support EIAV expression.

Purpose and Method of the Study

  • The main purpose of this research is to understand the role of monocyte maturation in controlling the expression of equine infectious anemia virus (EIAV).
  • To achieve this, the researchers developed an in vitro model wherein they infected freshly isolated, non-adherent equine peripheral blood monocytes with a strain of EIAV that typically affects macrophages. They then monitored the expression of EIAV in these cells over time.

Findings from the Study

  • The study observed a delay in viral antigen expression in the non-adherent cells. This indicates that viral expression is restricted in monocytes, raising the possibility that the maturation of monocytes into macrophages plays a vital role in EIAV replication.
  • Further supporting this hypothesis, nuclear run-on studies showed that the number of actively transcribed viral messages was nearly five times lower in monocyte cultures than in macrophage cultures by the fifth day post-infection.
  • Electrophoretic mobility shift assays identified three regions of the U3 enhancer that interacted with nuclear extracts from normal equine macrophages. Each of these regions contained the binding motif of a family of transcription factors associated with the proto-oncogene ets.
  • Transfection studies of ets motif mutants highlighted the significance of the U3 ets sites in regulating EIAV transcription within macrophages. This suggests that the specific interactions between the ets motif and nuclear extracts may be critical to enabling mature macrophages to better support EIAV replication.

Implications of the Findings

  • The different complexes formed by monocyte and macrophage nuclear extracts may explain why mature macrophages are better equipped to support EIAV expression.
  • The findings imply that manipulating monocyte maturation could potentially be a strategy to control the expression and replication of EIAV.
  • Freshly isolated, non-adherent equine monocytes may serve as a reservoir for EIAV, contributing to viral persistence in the host against the immune response.

Cite This Article

APA
Maury W. (1994). Monocyte maturation controls expression of equine infectious anemia virus. J Virol, 68(10), 6270-6279. https://doi.org/10.1128/JVI.68.10.6270-6279.1994

Publication

Journal of virology
ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 68
Issue: 10
Pages: 6270-6279

Researcher Affiliations

Maury, W
  • Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840.

MeSH Terms

  • Animals
  • Base Sequence
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Chloramphenicol O-Acetyltransferase / analysis
  • Chloramphenicol O-Acetyltransferase / biosynthesis
  • DNA Primers
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Viral
  • Glucosephosphate Dehydrogenase / analysis
  • Glucosephosphate Dehydrogenase / biosynthesis
  • Guanosine Triphosphate / metabolism
  • Horses
  • Humans
  • Infectious Anemia Virus, Equine / genetics
  • Infectious Anemia Virus, Equine / metabolism
  • Infectious Anemia Virus, Equine / physiology
  • Macrophages / microbiology
  • Macrophages / physiology
  • Molecular Sequence Data
  • Monocytes / microbiology
  • Monocytes / physiology
  • Mutagenesis, Site-Directed
  • Plasmids
  • Proto-Oncogene Mas
  • Repetitive Sequences, Nucleic Acid
  • Transcription, Genetic
  • Transfection
  • Virus Replication

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