Abstract
African swine fever, caused by African swine fever virus (ASFV), is a highly contagious hemorrhagic disease of domestic pigs. The current continent-wide pandemic has persisted for over 10 years, and its economy-devastating effect was highlighted after spreading to China, which possesses half of the world pig industry. So far, development of an effective and safe vaccine has not been finished largely due to the knowledge gaps in pathogenesis and immunology, particularly the role of cytokines in the host's immune response. Therefore, we performed experiments in domestic pigs to analyze the kinetics of representative circulating interferons (IFNs), interleukins (ILs), growth factors, tumor necrosis factors (TNFs), and chemokines induced by infection of type II virulent ASFV SY18. Pigs infected with this Chinese prototypical isolate developed severe clinical manifestations mostly from 3 days post inoculation (dpi) and died from 7 to 8 dpi. Serum analysis revealed a trend of robust and sustained elevation of pro-inflammatory cytokines including TNF-α, IFN-α, IL-1β, IL-6, IL-8, IL-12, IL-18, RANTES (regulated upon activation, normal T cell expressed and secreted), and IFN-γ-induced protein 10 (IP-10) from 3 dpi, but not the anti-inflammatory cytokines IL-10 and transforming growth factor-β (TGF-β). Moreover, secondary drastic increase of the levels of TNF-α, IL-1β, IL-6, and IL-8, as well as elevated IL-10, was observed at the terminal phase of infection. This pattern of cytokine secretion clearly drew an image of a typical cytokine storm characterized by delayed and dysregulated initiation of the secretion of pro-inflammatory cytokine and imbalanced pro- and anti-inflammatory response, which paved a way for further understanding of the molecular basis of ASFV pathogenesis.
Highlights
African swine fever (ASF), a highly hemorrhagic viral disease of domestic pigs, has been internationally epidemic for nearly 100 years ever since the first report in Africa in 1921 [1, 2]
We showed that cytokines such as IL1β, IL-6, tumor necrosis factors (TNFs)-α, IL-8, and IL-10 may act as indicators of a lethal outcome at the endpoint of the infection process
The major focus of our study was to characterize the kinetics of cytokines secreted in vivo, clarifying whether a cytokine storm was involved in the pathogenesis of African swine fever virus (ASFV)
Summary
African swine fever (ASF), a highly hemorrhagic viral disease of domestic pigs, has been internationally epidemic for nearly 100 years ever since the first report in Africa in 1921 [1, 2]. Besides soft ticks, which act as invertebrate competent vectors, ASFV just affects mammalian animals in the Suidae family, such as warthogs, wild boars, and domestic pigs. In contrast to the natural reservoir host warthogs, in which the infection of ASFV is basically asymptomatic [6], the domestic pigs and wild boars mostly develop severe clinical manifestations after virus invasion and present a mortality rate up to 100% roughly in 7–10 days post infection [7, 8], despite the fact that attenuated virus strains with low virulence may be isolated over an epidemic period in a certain naive region [9,10,11]
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