UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Recognition of viruses by the innate immune system.

Pichlmair, A.; (2008) Recognition of viruses by the innate immune system. Doctoral thesis , University of London. Green open access

[thumbnail of U592325.pdf] PDF
U592325.pdf

Download (14MB)

Abstract

When a cell gets infected with a virus, the innate immune system swings into action within minutes. The rapid production of pro-inflammatory cytokines and antivirally active type-I Interferons (IFN-a/p) is the most significant mechanism to limit virus spread. Two conceptually different pathogen recognition mechanisms are known that lead to antiviral responses through production of IFN-a/p: Specialised immune cells possess Toll-like receptors (TLRs), which sense incoming viruses in endosomes. Most other cells rely on the cytoplasmic RNA-helicases RIG-I and MDA5 that sense the presence of viruses within the cell. However, although proteins and signalling networks involved in innate recognition of viruses are well known, the exact molecular details of their interactions with the virus are only marginally understood. During my PHD thesis I dedicated myself to aid our understanding of virus recognition. I could show that recombinant lentiviruses are weak inducers of IFN-ct/p* in murine immune cells. Standard preparations of lentiviral vectors, however, are strong activators of the innate immune system. This activity is contained in tubulo-vesicular structures that are present within standard lentiviral preparations and have the ability to activate TLR9. Tubulo-vesicular structures can serve as adjuvant to facilitate adaptive immune responses and may therefore be important when considering lentiviral vectors for clinical applications. In my second project I focused on cytoplasmic virus recognition. Surprisingly, viral genomic single-stranded RNA from influenza virus can activate the cytoplasmic virus recognition receptor RIG-I. Unlike most cellular RNA species, single-stranded RNA from influenza and other viruses bear a 5' triphosphate group, which marks this RNA as 'foreign' and thereby induces interferon responses. Importantly, influenza virus codes for an interferon antagonist, the non-structural protein 1 (NS1), which forms a complex with RIG-I, suggesting that influenza virus specifically interferes with this pathway. In conclusion, the innate immune system employs diverse mechanisms to sense the presence of a virus through recognising diverse forms of viral nucleic acid.

Type: Thesis (Doctoral)
Title: Recognition of viruses by the innate immune system.
Identifier: PQ ETD:592325
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest. Third party copyright material has been removed from the ethesis
UCL classification:
URI: https://discovery.ucl.ac.uk/id/eprint/1445012
Downloads since deposit
155Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item