AUTHOR=Wang Shuchao , Zhang Jingyuan , Zhang Yanyan , Yang Jinjin , Wang Lidong , Qi Yu , Han Xun , Zhou Xintao , Miao Faming , Chen Teng , Wang Ying , Zhang Fei , Zhang Shoufeng , Hu Rongliang TITLE=Cytokine Storm in Domestic Pigs Induced by Infection of Virulent African Swine Fever Virus JOURNAL=Frontiers in Veterinary Science VOLUME=7 YEAR=2021 URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2020.601641 DOI=10.3389/fvets.2020.601641 ISSN=2297-1769 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.