In this study M-CSF differentiated human monocyte derived macrophages were used to investigate HIV-1 interactions with macrophage innate immune responses. Macrophages may be an important host cell for HIV-1. HIV-1 can infect and replicate within these cells without causing host cell cytopathicity unlike in T cells. Macrophages also aid in the spread of the virus and are likely to act as a viral reservoir protected from antivirals and immune responses due to the unique localisation of the virus within these cells. Surprisingly HIV-1 infection has little effect on the steady state transcriptome of MDM and despite the role of macrophages to detect incoming pathogens; no innate immune response to HIV-1 could be detected, in contrast with other viruses tested. The lack of immune response was not due to active viral suppression and addition of exogenous IFN or activation of the innate immune response at the time of HIV-1 infection can restrict viral infection in these cells, despite HIV-1 having a full complement of accessory proteins known to counteract IFN inducible restriction factors. This HIV-1 restriction induced by IFN was long lasting, likely for the lifetime of the MDM. IFN treatment of MDM with established HIV-1 infection however only transiently suppressed viral replication. Comparisons of MDM with other cell types which do show an innate immune IFN response to HIV-1 showed that MDM have relatively low levels of TLR7 gene expression, suggesting that MDM may lack one of the PRRs for detecting HIV-1. HIV-1 infection of MDM was found to attenuate NFκB activation in response to TLR stimulation and this attenuation could be reversed by priming the MDM with IFNγ. However this attenuation of the NFκB signal did not translate into decreased protein expression for a selection of proinflammatory cytokines examined.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:626728 |
| Date | January 2014 |
| Creators | Tsang, J. M. |
| Contributors | Noursadeghi, M. ; Miller, R. F. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1417140/ |
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