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Characterization of type 1 interferon production during persistent lymphocytic choriomeningitis virus (LCMV) infection.

Lee, L.N.; (2006) Characterization of type 1 interferon production during persistent lymphocytic choriomeningitis virus (LCMV) infection. Doctoral thesis , University of London. Green open access

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Abstract

Type 1 interferons (B5N-a/ps), are innate cytokines possessing important immunomodulatory and effector roles in the innate and adaptive response. They are transiently induced to very high levels during the initial stages of many viral infections. However, regulation of EFN-a/p production during persistent viral infections is not well understood. This project aimed to address these issues using the murine lymphocytic choriomeningitis virus (LCMV) infection model. Initial objectives were to develop assays that would allow characterisation of the EFN-a/p response during chronic LCMV infection in vivo and in vitro. Cell-based reporter gene assays were developed to measure IFN-a/p activity, along with a series of real-time quantitative reverse-transcriptase polymerase chain reaction assays to detect mRNA transcripts of IFN-a/p, and their utility was evaluated. Analysis of IFN-a/p production during acute and chronic LCMV infection indicated that there was an early burst of IFN production following infection, but only a low level of IFN-a/p production could be detected during the chronic phase of LCMV infection despite ongoing viral replication. Persistently-infected mice exhibited reduced numbers of splenic CD1 lc+ plasmacytoid dendritic cells (DC). These animals were able to produce IFN-a/p in response toll-like-receptor (TLR) stimuli. Inoculation of influenza virus elicited less IFN-a/p production than was observed in uninfected mice, but this may have been due to impairment of influenza virus replication in persistently-infected mice. In vitro LCMV infection of DC and fibroblast cell lines induced very little IFN-a/p production. Persistently-infected animals made normal IFN-a/p responses to TLR ligands but produced lower levels of IFN-a/p upon infection with Sendai virus than uninfected cells. There are several pathways by which IFN-a/p can be induced. These results suggest that the intracellular response to RNA viruses may be impaired in LCMV-infected cells, although persistently-infected cells still retain some capacity to respond to external TLR stimuli.

Type: Thesis (Doctoral)
Title: Characterization of type 1 interferon production during persistent lymphocytic choriomeningitis virus (LCMV) infection.
Identifier: PQ ETD:593058
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by Proquest
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/1445734
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