Pulsed stable isotope labeling of amino acids in cell culture uncovers the dynamic interactions between HIV-1 and the monocyte-derived macrophage

Stephanie D. Kraft-Terry, Ian L. Engebretsen, Dhundy Raj Bastola, Howard S Fox, Pawel S Ciborowski, Howard Eliot Gendelman

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Dynamic interactions between human immunodeficiency virus-1 (HIV-1) and the macrophage govern the tempo of viral dissemination and replication in its human host. HIV-1 affects macrophage phenotype, and the macrophage, in turn, can modulate the viral life cycle. While these processes are linked to host-cell function and survival, the precise intracellular pathways involved are incompletely understood. To elucidate such dynamic virus-cell events, we employed pulsed stable isotope labeling of amino acids in cell culture. Alterations in de novo protein synthesis of HIV-1 infected human monocyte-derived macrophages (MDM) were examined after 3, 5, and 7 days of viral infection. Synthesis rates of cellular metabolic, regulatory, and DNA packaging activities were decreased, whereas, those affecting antigen presentation (major histocompatibility complex I and II) and interferon-induced antiviral activities were increased. Interestingly, enrichment of proteins linked to chromatin assembly or disassembly, DNA packaging, and nucleosome assembly were identified that paralleled virus-induced cytopathology and replication. We conclude that HIV-1 regulates a range of host MDM proteins that affect its survival and abilities to contain infection.

Original languageEnglish (US)
Pages (from-to)2852-2862
Number of pages11
JournalJournal of Proteome Research
Volume10
Issue number6
DOIs
StatePublished - Jun 3 2011

Fingerprint

Isotope Labeling
Macrophages
Viruses
Cell culture
Isotopes
Labeling
HIV-1
Cell Culture Techniques
Amino Acids
DNA Packaging
Packaging
Proteins
Chromatin Assembly and Disassembly
Nucleosomes
Antigen Presentation
Virus Diseases
Life Cycle Stages
Major Histocompatibility Complex
DNA
Interferons

Keywords

  • cell function
  • human immunodeficiency virus
  • monocyte-derived macrophages
  • proteome
  • pulsed stable isotope labeling of amino acids in cell culture

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

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abstract = "Dynamic interactions between human immunodeficiency virus-1 (HIV-1) and the macrophage govern the tempo of viral dissemination and replication in its human host. HIV-1 affects macrophage phenotype, and the macrophage, in turn, can modulate the viral life cycle. While these processes are linked to host-cell function and survival, the precise intracellular pathways involved are incompletely understood. To elucidate such dynamic virus-cell events, we employed pulsed stable isotope labeling of amino acids in cell culture. Alterations in de novo protein synthesis of HIV-1 infected human monocyte-derived macrophages (MDM) were examined after 3, 5, and 7 days of viral infection. Synthesis rates of cellular metabolic, regulatory, and DNA packaging activities were decreased, whereas, those affecting antigen presentation (major histocompatibility complex I and II) and interferon-induced antiviral activities were increased. Interestingly, enrichment of proteins linked to chromatin assembly or disassembly, DNA packaging, and nucleosome assembly were identified that paralleled virus-induced cytopathology and replication. We conclude that HIV-1 regulates a range of host MDM proteins that affect its survival and abilities to contain infection.",
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AU - Fox, Howard S

AU - Ciborowski, Pawel S

AU - Gendelman, Howard Eliot

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