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 K. Bastola, Howard S. Fox, Pawel Ciborowski, Howard E. Gendelman

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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

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)

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