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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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Related in: MedlinePlus

Heatmap of log2 (H/M ratio) labeled by their gene name. Expression between days 3, 5, and 7 is colored with varying intensities ranging from blue to red; blue being the lowest ratio, red being the highest ratio, and yellow representing those ratios that equal one.
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fig6: Heatmap of log2 (H/M ratio) labeled by their gene name. Expression between days 3, 5, and 7 is colored with varying intensities ranging from blue to red; blue being the lowest ratio, red being the highest ratio, and yellow representing those ratios that equal one.

Mentions: The cytopathology of HIV-1 infected MDM has been the topic of previous studies investigating cytoskeletal transformation, multinucleated giant cell formation, and HIV-1-associated neurodegeneration.8,35 Less studied are the protein changes resulting in these cytopathological findings. The epigenetic control of HIV-1 viral latency has been the subject of many recent studies and helps to explain the cytopathicity of HIV-1 infection. While histone methylation, acetylation and deacetylation are utilized to control viral integration and expression,(48) histone synthesis and turnover is an area that has not been heavily investigated in relation to HIV-1 infection. We identified differential regulation in the synthesis rates of histone proteins, which are seen in our significant GO groupings (Figure 6). Significant down-regulation in synthesis rates were identified in some histones by D3 post infection, and further down-regulation in the rates of protein synthesis were identified by days 5 and 7 following infection. Such a response is made when the host cell works to restrict viral dissemination in MDM. Indeed, histone recycling during transcription is thought to occur when it is necessary to replace modified histones, such as those that are methylated.(49)


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)

Heatmap of log2 (H/M ratio) labeled by their gene name. Expression between days 3, 5, and 7 is colored with varying intensities ranging from blue to red; blue being the lowest ratio, red being the highest ratio, and yellow representing those ratios that equal one.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Heatmap of log2 (H/M ratio) labeled by their gene name. Expression between days 3, 5, and 7 is colored with varying intensities ranging from blue to red; blue being the lowest ratio, red being the highest ratio, and yellow representing those ratios that equal one.
Mentions: The cytopathology of HIV-1 infected MDM has been the topic of previous studies investigating cytoskeletal transformation, multinucleated giant cell formation, and HIV-1-associated neurodegeneration.8,35 Less studied are the protein changes resulting in these cytopathological findings. The epigenetic control of HIV-1 viral latency has been the subject of many recent studies and helps to explain the cytopathicity of HIV-1 infection. While histone methylation, acetylation and deacetylation are utilized to control viral integration and expression,(48) histone synthesis and turnover is an area that has not been heavily investigated in relation to HIV-1 infection. We identified differential regulation in the synthesis rates of histone proteins, which are seen in our significant GO groupings (Figure 6). Significant down-regulation in synthesis rates were identified in some histones by D3 post infection, and further down-regulation in the rates of protein synthesis were identified by days 5 and 7 following infection. Such a response is made when the host cell works to restrict viral dissemination in MDM. Indeed, histone recycling during transcription is thought to occur when it is necessary to replace modified histones, such as those that are methylated.(49)

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