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Title: The role of interferon-regulated genes in the control of African swine fever virus replication
Author: Golding, Josephine P.
ISNI:       0000 0004 5348 343X
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2014
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African swine fever virus (ASFV) replicates primarily in blood monocytes and macrophages in the lymphoid tissues and organs. Type I interferon (IFN) participates in the host innate immune response to viral infection. IFN regulates the expression of many different genes, known as IFN-stimulated genes that restrict viral replication, including the Mx genes. Using the MDBKt2/MxCAT bioassay, an assay used to detect Type I IFN (lFNu/P), the induction of biologically active IFN occurring during in vivo infection with virulent ASFV strains OURT8811 and Georgia 200711 was observed. There was no detection of biologically active IFN during infection with the avirulent strain OURT88/3. The effect of recombinant porcine IFNul (rpoIFNul) on ASFV replication in porcine macrophages was assessed. Only the replication of avirulent OURT88/3 was affected by the pre-treatment of rpoIFNu 1. Virulent strains Georgia 200711, OURT8811 and Pr4 were unaffected by the rpoIFNul -induced antiviral state. Multigene families (MGF), MGF 360 and MGF 5051530 have been implicated in evasion of the antiviral effects of IFN. The replication of recombinant Pr4~35 strain, which lacks six genes ofMGF 360, and two genes from MGF 5051530, was reduced in rpoIFNul treated cells, compared to untreated cells. The MGF genes missing in the Pr4~35 strain is similar to the avirulent OURT88/3 strain. Porcine Mx 1 has been shown to associate with ASFV replication sites, and human MxA has been shown to inhibit viral replication of tissue-adapted strain BA 71 V. SiRNA knockdown of Mxl was carried out in pre-treated rpoIFNul alveolar macrophages, and preliminary data suggests that Mx 1 is not essential for inhibiting the avirulent OURT88/3 strain. A human embryonic kidney cell line expressing the human IFN-stimulated gene viperin reduced ASFV DNA replication while not affecting infectivity of the virus. ASFV capsid protein pE120R was reduced in viperin expressing cells. This suggests that IFN-stimulated gene viperin can target ASFV replication, although the mechanism has not been determined.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available