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HIV-1 infection of macrophages is dependent on evasion of innate immune cellular activation

Tsang, J; Chain, BM; Miller, RF; Webb, BLJ; Barclay, W; Towers, GJ; Katz, DR; (2009) HIV-1 infection of macrophages is dependent on evasion of innate immune cellular activation. AIDS , 23 (17) 2255 - 2263. 10.1097/QAD.0b013e328331a4ce.

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Abstract

Objective: The cellular innate immune response to HIV-1 is poorly characterized. In view of HIV-1 tropism for macrophages, which can be activated via pattern recognition receptors to trigger antimicrobial defences, we investigated innate immune responses to HIV-1 by monocyte-derived macrophages.Design: In a model of productive HIV-1 infection, cellular innate immune responses to HIV-1 were investigated, at the level of transcription factor activation, specific gene expression and genome-wide transcriptional profiling. In addition, the viral determinants of macrophage responses and the physiological effect of innate immune cellular activation on HIV-1 replication were assessed.Results: Productive HIV-1 infection did not activate nuclear factor-kappa B and interferon regulatory factor 3 transcription factors or interferon gene expression (IFN) and caused remarkably small changes to the host-cell transcriptome, with no evidence of inflammatory or IFN signatures. Evasion of IFN induction was not dependent on HIV-1 envelope-mediated cellular entry, inhibition by accessory proteins or reverse transcription of ssRNA that may reduce innate immune cellular activation by viral RNA. Furthermore, IFN beta priming did not sensitize responses to HIV-1. Importantly, exogenous IFN beta or stimulation with the RNA analogue poly I:C to simulate innate immune activation invoked HIV-1 restriction.Conclusion: We conclude that macrophages lack functional pattern recognition receptors for this virus and that HIV-1 tropism for macrophages helps to establish a foothold in the host without triggering innate immune cellular activation, which would otherwise block viral infection effectively. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Type: Article
Title: HIV-1 infection of macrophages is dependent on evasion of innate immune cellular activation
DOI: 10.1097/QAD.0b013e328331a4ce
Publisher version: http://doi.org/10.1097/QAD.0b013e328331a4ce
Language: English
Keywords: HIV-1, innate immunity, interferons, macrophages, pattern recognition receptors
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health > Infection and Population Health
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: http://discovery.ucl.ac.uk/id/eprint/164900
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