Establishing a role for intrinsic immunity to influenza A virus infection

Charman, Matthew (2017) Establishing a role for intrinsic immunity to influenza A virus infection. PhD thesis, University of Glasgow.

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Antiviral host factors constitutively expressed to high levels can confer intrinsic
immunity. Unlike, induced antiviral responses, these pre-existing intrinsic
defences can protect cells against the initial stages of virus infection. However,
there has been little investigation into the existence of such defences at
mucosal surfaces, major portals of virus entry. Accordingly, a role for intrinsic
immunity to influenza A virus (IAV) infection of the lung and respiratory tract is
yet to be established. We therefore set out to investigate the hypothesis that
constitutive expression of key antiviral host factors in cells of the lung and
respiratory tract may confer intrinsic immunity to IAV infection. We focused on
the TRIpartite Motif (TRIM) proteins, a family known to play a role in multiple
aspects of host immunity to virus infection. By analysing a cell line of lung origin
restrictive to IAV plaque formation, we identified constitutive expression of
TRIM22, an antiviral effector and interferon stimulated gene (ISG) product
reported to restrict a number of viruses as part of an innate immune response,
including IAV. Analysis of open source data, respiratory tissues, and cultured cell
lines, demonstrated that TRIM22 was constitutively expressed to high levels in
cells of the respiratory epithelium, independently of IAV infection. By depleting
TRIM22 in a cell culture model of constitutive expression, we investigated
whether constitutive TRIM22 expression confers an intrinsic defence against IAV
infection. We found that TRIM22 supresses IAV gene expression, inhibiting the
initiating cycle of IAV replication. Reconstitution of TRIM22 expression in a cell
line deficient in TRIM22 supressed the expression of foreign reporter genes in a
SPRY domain-dependent manner, suggesting a potential mechanism by which
TRIM22 may restrict the infection of multiple viruses. Together, our data
demonstrate that TRIM22 confers intrinsic immunity to IAV infection in the
respiratory tract, thereby establishing an important role for intrinsic immunity in
the regulation of IAV infection.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Intrinsic immunity, influenza A virus, TRIM22.
Subjects: Q Science > QR Microbiology
Q Science > QR Microbiology > QR355 Virology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Supervisor's Name: Boutell, Dr. Chris
Date of Award: 2017
Embargo Date: 11 September 2020
Depositing User: Mr Matthew J G Charman
Unique ID: glathesis:2017-8384
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 29 Sep 2017 12:12
Last Modified: 22 Nov 2017 10:01

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