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Related Concept Videos

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Size and Structure of Viral Genomes

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Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1
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Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1

Published on: September 5, 2016

Human macrophages support persistent transcription from unintegrated HIV-1 DNA.

Jeremy Kelly1, Margaret H Beddall, Dongyang Yu

  • 1Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110, USA.

Virology
|December 7, 2007
PubMed
Summary

Unintegrated human immunodeficiency virus (HIV) DNA is surprisingly stable and biologically active in macrophages, unlike in T cells. This persistent viral DNA drives chemokine production, offering new insights into HIV persistence.

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Single-cell Quantitation of mRNA and Surface Protein Expression in Simian Immunodeficiency Virus-infected CD4+ T Cells Isolated from Rhesus macaques

Published on: September 25, 2018

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Retroviruses, including HIV, typically require genome integration for stability and replication.
  • In resting CD4 T cells, impaired integration limits HIV DNA activity and survival.
  • Unintegrated HIV DNA diminishes rapidly in dividing T cells.

Purpose of the Study:

  • To investigate the stability and biological activity of unintegrated HIV DNA in macrophages.
  • To explore viral gene transcription and protein synthesis from unintegrated HIV DNA in macrophages.
  • To determine if HIV infection of macrophages generates chemokines independently of integration.

Main Methods:

  • In vitro HIV infection of primary human macrophages.
  • Analysis of unintegrated viral DNA forms (linear, 1-LTR, 2-LTR circles) over time.
  • Quantification of viral gene transcription and protein synthesis (Nef).
  • Measurement of chemokine production by infected macrophages.

Main Results:

  • Unintegrated HIV DNA (linear, 1-LTR, 2-LTR circles) demonstrated remarkable stability in macrophages for at least 30 days.
  • Persistent, selective viral gene transcription occurred, favoring early genes like nef and tat.
  • The viral protein Nef was measurably synthesized from unintegrated DNA.
  • HIV infection of macrophages induced the generation of numerous chemokines, independent of viral integration.

Conclusions:

  • Macrophages provide a unique cellular environment supporting the stability and biological activity of unintegrated HIV DNA.
  • Persistent transcription and Nef synthesis from unintegrated HIV DNA contribute to viral persistence and potentially host immune modulation.
  • HIV-induced chemokine production in macrophages may play a role in viral pathogenesis and dissemination.