Virus Expression Database

GSE13395

HIV-1 Activates Macrophages Independent of Toll-like Receptors

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

16 Samples

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