Submitted by Maureen M Goodenow (University of Florida, USA) on Oct 29 2008
Platform: microarray – [HG_U95Av2] Affymetrix Human Genome U95 Version 2 Array
Pubmed: 19048100
Summary Macrophages provide an interface between innate and adaptive immunity and are important long-lived reservoirs for Human Immunodeficiency Virus Type-1 (HIV-1). Multiple genetic networks involved in regulating signal transduction cascades and immune responses in macrophages are coordinately modulated by HIV-1 infection. To evaluate complex interrelated processes and to assemble an integrated view of activated signaling networks, a systems biology strategy was applied to genomic and proteomic responses by primary human macrophages over the course of HIV-1 infection. Macrophage responses, including cell cycle, calcium, apoptosis, mitogen-activated protein kinases (MAPK), and cytokines/chemokines, to HIV-1 were temporally regulated, in the absence of cell proliferation. In contrast, Toll-like receptor (TLR) pathways remained unaltered by HIV-1, although TLRs 3, 4, 7, and 8 were expressed and responded to ligand stimulation in macrophages. HIV-1 failed to activate phosphorylation of IRAK-1 or IRF-3, modulate intracellular protein levels of Mx1, an interferon-stimulated gene, or stimulate secretion of TNF, IL-1b, or IL-6. Activation of pathways other than TLR was inadequate to stimulate, via cross-talk mechanisms through molecular hubs, the production of proinflammatory cytokines typical of a TLR response. HIV-1 sensitized macrophage responses to TLR ligands, and the magnitude of viral priming was related to virus replication. HIV-1 induced a primed, proinflammatory state, M1HIV, which increased the responsiveness of macrophages to TLR ligands. HIV-1 might passively evade pattern recognition, actively inhibit or suppress recognition and signaling, or require dynamic interactions between macrophages and other cells, such as lymphocytes or endothelial cells. HIV-1 evasion of TLR recognition and simultaneous priming of macrophages may represent a strategy for viral survival, contribute to immune pathogenesis, and provide important targets for therapeutic approaches.
Affymetrix arrays were used to identify genomic macrophage response to HIV during viral spread in culture.
Keywords: time course
ID | Title | Cell Type | Timepoint | Reported Virus | Virus Species | Exclusion Reason |
---|---|---|---|---|---|---|
GSM338256 | Macrophage Infected Day4 Rep1 | macrophage | 4 days | HIV-1 | Human immunodeficiency virus 1 | Data failed QC Platform not specified in raw data |
GSM338257 | Macrophage Infected Day7 Rep1 | macrophage | 7 days | HIV-1 | Human immunodeficiency virus 1 | Data failed QC Platform not specified in raw data |
GSM338258 | Macrophage Mock Day4 Rep1 | macrophage | 4 days | Mock | Uninfected | Data failed QC Platform not specified in raw data |
GSM338259 | Macrophage Mock Day7 Rep1 | macrophage | 7 days | Mock | Uninfected | Data failed QC Platform not specified in raw data |
GSM338260 | Macrophage Infected Day4 Rep2 | macrophage | 4 days | HIV-1 | Human immunodeficiency virus 1 | Data failed QC Platform not specified in raw data |
GSM338261 | Macrophage Infected Day7 Rep2 | macrophage | 7 days | HIV-1 | Human immunodeficiency virus 1 | Data failed QC Platform not specified in raw data |
GSM338262 | Macrophage Mock Day4 Rep2 | macrophage | 4 days | Mock | Uninfected | Data failed QC Platform not specified in raw data |
GSM338263 | Macrophage Mock Day7 Rep2 | macrophage | 7 days | Mock | Uninfected | Data failed QC Platform not specified in raw data |
GSM338264 | Macrophage Infected Day2 Rep3 | macrophage | 2 days | HIV-1 | Human immunodeficiency virus 1 | Data failed QC Platform not specified in raw data |
GSM338265 | Macrophage Infected Day4 Rep3 | macrophage | 4 days | HIV-1 | Human immunodeficiency virus 1 | Data failed QC Platform not specified in raw data |
GSM338266 | Macrophage Infected Day7 Rep3 | macrophage | 7 days | HIV-1 | Human immunodeficiency virus 1 | Data failed QC Platform not specified in raw data |
GSM338267 | Macrophage Mock Day2 Rep3 | macrophage | 2 days | Mock | Uninfected | Data failed QC Platform not specified in raw data |
GSM338268 | Macrophage Mock Day4 Rep3 | macrophage | 4 days | Mock | Uninfected | Data failed QC Platform not specified in raw data |
GSM338269 | Macrophage Mock Day7 Rep3 | macrophage | 7 days | Mock | Uninfected | Data failed QC Platform not specified in raw data |
GSM338270 | Macrophage Infected Day2 Rep4 | macrophage | 2 days | HIV-1 | Human immunodeficiency virus 1 | Data failed QC Platform not specified in raw data |
GSM338271 | Macrophage Mock Day2 Rep4 | macrophage | 2 days | Mock | Uninfected | Data failed QC Platform not specified in raw data |