The ATF6 branch of unfolded protein response and apoptosis are activated to promote African swine fever virus infection

Galindo, I; Hernáez, B; Muñoz-Moreno, R; Cuesta-Geijo, M A; Dalmau-Mena, I; Alonso, C

ASFV infection leads to the induction of ER chaperones. The induction of caspase 12 after ASFV infection suggests that the virus triggers an ER stress response. This response is an autoregulatory program that upregulates a large number of genes, such as ER chaperones and ER-associated degradation (ERAD) components, which increase the folding capacity of the ER. 26 In order to determine whether ASFV infection induces this response, we used western blot analysis to monitor the expression levels of the ER chaperones BiP, calreticulin, calnexin, ERp57 and PDI (protein disulfide isomerase) over the course of the infection. Calreticulin and calnexin were induced upon ASFV infection at 16 hpi (Figure 4a ), while only a modest increase in PDI levels was found at 48 hpi. Interestingly, ASFV did not induce the expression of ERp57 or BiP. Chaperone upregulation was coincident with the expression of viral protein p30. Actin levels remained constant during the course of the infection, indicating that chaperone induction was not caused by a global upregulation of protein translation. We also analyzed the expression of BiP by inmunofluorescence. Cells treated with tunicamycin showed a typical ER pattern for BiP, while BiP expression was undetectable in non-treated/non-infected controls and infected cells (Figure 4c ). This could be probably due to the low levels of BiP to be detected by the antibody.