Franzoni, Giulia (2017) Interaction of monocytes and derived macrophage subsets with African swine fever viruses of diverse virulence. Doctoral Thesis.
African swine fever (ASF) is a devastating disease for which there is no vaccine available. The ASF virus (ASFV) primarily infects cells of the myeloid lineage and this tropism is thought to be crucial for disease pathogenesis. A detailed in vitro characterization of the interactions of a virulent (22653/14) and a tissue culture adapted (BA71V) strains of ASFV with porcine monocytes, un-activated (moM0), classically (moM1) and alternatively (moM2) activated monocyte-derived macrophages was conducted to better understand this relationship. Low concentration of hM-CSF was selected as the method of choice to generate moM0. Using a multiplicity-of-infection (MOI) of 1, both viruses were able to infect monocytes and macrophage subsets, but BA71V presented a reduced ability to infect moM1 compared to 22653/14, with higher expression of early compared to late proteins. Using an MOI of 0.01, only 22653/14 was able to replicate in all the macrophage subsets, with initially lowest in moM1 and moM2 ASFV down-regulated CD16 expression and BA71V-infected but not 22653/14-infected moM0 and moM2 presented with a reduced expression of MHC class I. Higher levels of IL-18, IL-1alpha and IL-1beta were released from moM1 after infection with BA71V. These results revealed differences between these strains, suggesting that virulent isolates have evolved mechanisms to counteract activated macrophages responses, promoting their survival, dissemination in the host and so ASF pathogenesis.
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