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Title: Role of BPIFA1/SPLUNC1 in the pathogenesis and immune response against influenza A virus in mice
Author: Al Katy, Sanaria
ISNI:       0000 0004 9358 3611
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2019
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The epithelial layer of the respiratory system has a critical and fundamental role in the defence against microbes via the secretion of a number of proteins that function in the process of host innate defence. One such protein, bactericidal/permeabilityincreasing fold-containing family member-A1 (Bpifa1) is secreted by the epithelium of the respiratory tract, and has previously been implicated in the inhibition of binding and entry of influenza A virus (IAV). However, its precise biological functions remain unclear. In order to investigate the role of Bpifa1 during IAV infection, in vivo expression of recombinant mouse Bpifa1 and human BPIFA1 using a mammalian expression vector was attempted. Unfortunately, though Bpifa1 was successfully expressed in vitro, no in vivo expression could be elicited. Instead, the role of Bpifa1 in the transmission of IAV and the associated immune response were explored using a mouse model. For this purpose, control wild-type C57BL/6J and Bpifa1-/- mice were infected with IAV using different virus doses at high or low and subjected to a transmission study. It was found that Bpifa1-/- mice were more susceptible to transmission and showed deficient IgA production, especially at low dose infection. The histological changes were similar in all groups, though more severe in Bpifa1-/-mice and at high dose. IAV infection of the nasal cavity and the associated loss of epithelial cells was more pronounced in Bpifa1-/-mice, in addition to mononuclear mucosal infiltration and nasal-associated lymphoid tissue (NALT) formation. Importantly, this study highlights that IAV transmitted more frequently and efficiently to Bpifa1-/- mice, indicating a role for Bpifa1 in protection from IAV infection and the efficient generation of virus-specific IgA in the respiratory tract. The work presented in this thesis indicates for the first time that Bpifa1 has an important role not only in innate immune defence but also in the adaptive immune response against IAV.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral