Mosquito transmitted viruses (arboviruses) cause significant burden in much of the developing world. Little is known about mosquito responses to viral infection, and how these responses could be utilised to prevent spread of viral disease. Anopheles gambiae, the principal vector of human malaria, unusually transmits virtually no arboviruses, with one known exception - O’nyony-nyong Virus (ONNV). In this thesis the interactions between ONNV and the A. gambiae immune system were studied. Initially ONNV infection in A. gambiae mosquitoes and an A. gambiae derived cell line were characterised. The in vivo transcriptional responses of A. gambiae to viral infection were profiled using full genome microarrays, describing the global response to ONNV infection. This thesis demonstrates that the A. gambiae immune system does respond to viral infection, with genes covering all aspects of immunity being differentially regulated, from pathogen recognition to modulation of immune signalling, complement-mediated lysis/opsonisation and immune effector mechanisms. Furthermore, this study identified four immune genes (a galectin, an MD2-like receptor and two lysozymes) regulated by ONNV infection that are capable of limiting virus during infection. These genes have novel roles in anti-viral immunity, and suggest previously uncharacterised mechanisms for targeting viral infection. Additionally, it is shown that A. gambiae uses a combination of core conserved anti-viral mechanisms, including RNAi, but does not utilise some signalling pathways reported to be anti-viral in other insects. This indicates that species specific mechanisms target viral infection. Finally this study demonstrates that foreign RNA acts as a Pathogen Associated Molecular Pattern (PAMP) in A. gambiae derived cells, and triggers transcriptional responses that dramatically reduce viral infection. In conclusion the data presented in this thesis demonstrate that A. gambiae responds to and is capable of limiting viral infection through conserved and novel immune mechanisms triggered by recognition of viral infection and foreign RNA.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:528737 |
| Date | January 2010 |
| Creators | Waldock, Joanna |
| Contributors | Christophides, George |
| Publisher | Imperial College London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/10044/1/6358 |
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