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

Kraft-Terry SD, Engebretsen IL, Bastola DK, Fox HS, Ciborowski P, Gendelman HE - J. Proteome Res. (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198-5880, USA.

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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Enriched protein classifications for the correlation network in Supplemental Figure 2 (Supporting Information).
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fig5: Enriched protein classifications for the correlation network in Supplemental Figure 2 (Supporting Information).

Mentions: MaxQuant protein groups were also examined in parallel for interactions between one another and to provide confirmation and extensions of the protein maps. Indeed, by performing cluster analysis, we selected two clusters that included interactions from highly significant groupings that are linked to macrophage functions. The first cluster demonstrates specific interactions between DNA packaging, chromatin assembly/disassembly, and nucleosome assembly, along with fatty acid oxidation and antigen processing and presentation (Figure 5, Supplemental Figure 2, Supporting Information). In the second cluster, we identified interactions that appeared to split between two distinct groups (Supplemental Figures 3 and 4, Supporting Information). The first was between transcription initiation, nucleosome assembly, chromatin assembly/disassembly, DNA packaging, second messenger signaling and phosphoinositide-mediated signaling. The second was involved in the immune system and developmental regulation, including negative regulation of cellular differentiation, regulation of immune system processes, myeloid cell differentiation, megakaryocyte differentiation, hemopoiesis, and immune system development. A third, but less significant, contributor was the regulation of ubiquitin-protein ligase activity (both positive and negative).


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

Kraft-Terry SD, Engebretsen IL, Bastola DK, Fox HS, Ciborowski P, Gendelman HE - J. Proteome Res. (2011)

Enriched protein classifications for the correlation network in Supplemental Figure 2 (Supporting Information).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108467&req=5

fig5: Enriched protein classifications for the correlation network in Supplemental Figure 2 (Supporting Information).
Mentions: MaxQuant protein groups were also examined in parallel for interactions between one another and to provide confirmation and extensions of the protein maps. Indeed, by performing cluster analysis, we selected two clusters that included interactions from highly significant groupings that are linked to macrophage functions. The first cluster demonstrates specific interactions between DNA packaging, chromatin assembly/disassembly, and nucleosome assembly, along with fatty acid oxidation and antigen processing and presentation (Figure 5, Supplemental Figure 2, Supporting Information). In the second cluster, we identified interactions that appeared to split between two distinct groups (Supplemental Figures 3 and 4, Supporting Information). The first was between transcription initiation, nucleosome assembly, chromatin assembly/disassembly, DNA packaging, second messenger signaling and phosphoinositide-mediated signaling. The second was involved in the immune system and developmental regulation, including negative regulation of cellular differentiation, regulation of immune system processes, myeloid cell differentiation, megakaryocyte differentiation, hemopoiesis, and immune system development. A third, but less significant, contributor was the regulation of ubiquitin-protein ligase activity (both positive and negative).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198-5880, USA.

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.

Show MeSH
Related in: MedlinePlus