title: Pulsed stable isotope labeling of amino acids in cell culture uncovers the dynamic interactions between HIV-1 and the monocyte-derived macrophage.
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.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198-5880, USA.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Kraft-Terry
authors.forename: Ian L
authors.initials: IL
authors.lastname: Engebretsen
authors.forename: Dhundy K
authors.initials: DK
authors.lastname: Bastola
authors.forename: Howard S
authors.initials: HS
authors.lastname: Fox
authors.forename: Pawel
authors.initials: P
authors.lastname: Ciborowski
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D016655:HIV Core Protein p24 / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007372:Interferons / Q000378:metabolism; D007553:Isotope Labeling; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D009000:Monocytes / Q000166:cytology*; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D000596:Amino Acids; D016655:HIV Core Protein p24; D020543:Proteome; D007372:Interferons