African Swine Fever Virus Infection Induces Tumor Necrosis Factor Alpha Production: Implications in Pathogenesis

Abstract

We have analyzed the production of tumor necrosis factor alpha (TNF-α) induced by in vitro infection with African swine fever (ASF) virus (ASFV) and the systemic and local release of this inflammatory cytokine upon in vivo infection. An early increase in TNF-α mRNA expression was detected in ASFV-infected alveolar macrophages, and high levels of TNF-α protein were detected by ELISA in culture supernatants from these cells. When animals were experimentally infected with a virulent isolate (E-75), enhanced TNF-α expression in mainly affected organs correlated with viral protein expression. Finally, elevated levels of TNF-α were detected in serum, corresponding to the onset of clinical signs. TNF-α has been reported to be critically involved in the pathogenesis of major clinical events in ASF, such as intravascular coagulation, tissue injury, apoptosis, and shock. In the present study, TNF-α containing supernatants from ASFV-infected cultures induced apoptosis in uninfected lymphocytes; this effect was partially abrogated by preincubation with an anti-TNF-α specific antibody. These results suggest a relevant role for TNF-α in the pathogenesis of ASF.

Live attenuated African swine fever viruses as ideal tools to dissect the mechanisms involved in viral pathogenesis and immune protection

“…The control of the infection by pigs vaccinated with 10 4 HAU 50 of E75CV1 correlated with the control of the cytokine storm typically triggered by virulent ASFV strains such as E75. Thus, the levels of IFN-α (Figure 8 A) and TNF-α (Figure 8 B) in pig sera remained at very low or undetectable levels in protected animals, while control animals showed an exponential increase in the sera levels of both cytokines after lethal challenge with the homologous E75 virulent ASFV strain, as was previously described, at least for TNF-α [ 37 ]. Besides these two cytokines, several other soluble factors were found at high levels in sera from severely ASF-affected pigs by day 7 pi with E75, including IL-12 and IL-1β (data not shown) and for the first time, also for sCD163 (Figure 8 C), an activation macrophage marker that has been associated with several chronic inflammatory diseases, sepsis, and more recently also with certain haemorrhagic fever diseases caused by viruses [ 38 ].…”

Living with the enemy or uninvited guests: Functional genomics approaches to investigating host resistance or tolerance traits to a protozoan parasite, Theileria annulata, in cattle

“…All of these pathogens induce similar clinical signs including fever, anaemia, inappetence, and cachexia and are often fatal, within a few days of infection. These clinical signs in the non-adapted hosts are similar to those induced by high levels of pro-inflammatory cytokines, akin to a cytokine storm (Zhang et al, 2004;de Jong et al, 2006;Wauquier et al, 2010;Gomez Del Moral et al, 1999). Similar clinical signs are seen in cattle in response to the tick-borne protozoan parasite, T. annulata.…”

African swine fever virus infection in Classical swine fever subclinically infected wild boars

“…It is known that ASFV activates monocytes/macrophages that secrete a wide range of mediators including pro-inflammatory cytokines such as IL-6 and TNF-α [ 47 – 49 ], which can trigger acute phase reactions, inflammation, activation of endothelial cells and apoptosis. Paradoxically, the absence of IL-6 and TNF- α was detected in the sera from both experimentally infected groups.…”