https://orcid.org/0000-0002-4258-0651
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Luise Brose, Alexander Schäfer, Kati Franzke, Clemens Cammann, Ulrike Seifert, Gang Pei, Sandra Blome, Michael R Knittler, Ulrike Blohm, Virulent African swine fever virus infection of porcine monocytes causes SLA I subversion due to loss of proper ER structure/function, The Journal of Immunology, Volume 214, Issue 3, March 2025, Pages 532–550, https://doi.org/10.1093/jimmun/vkae063
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Abstract
African swine fever virus (ASFV) is a large DNA virus of the Asfarviridae family that causes a fatal hemorrhagic disease in domestic swine and wild boar. Infections with moderately virulent strains predominantly result in a milder clinical course and lower lethality. As target cells of ASFV, monocytes play a crucial role in triggering T-cell-mediated immune defense and ASF pathogenesis. We compared the effect of the highly virulent “Armenia2008” (ASFV-A) virus strain with that of the naturally attenuated “Estonia2014” (ASFV-E) on cellular immune activation in vivo and on primary monocytes ex vivo. Specifically, we asked whether antigen presentation of porcine monocytes is impaired upon ASFV-A infection. ASFV-A-infected monocytes are characterized by lower levels of swine leukocyte antigen (SLA) class I on the cell surface than ASFV-E-infected and uninfected monocytes. Despite stable steady-state SLA I mRNA/protein levels and expression of critical components of the antigen processing machinery, a marked decrease in maturation and reduced surface transport of SLA I were observed in ASFV-A-infected monocytes. The intracellular maturation block of SLA I was accompanied by a loss of functional rough ER structures and a pronounced formation of ER-associated aggresomes. This unsolved cellular stress resulted in a shutdown of overall host cell protein translation, mitochondrial dysfunction, and caspase-3-mediated apoptosis. In contrast, no such cellular subversion phenomenon was found in ASFV-E-infected monocytes. Our findings suggest that in domestic pigs infected with highly virulent ASFV-A, sequential subversion events occur in infected monocytes, likely leading to compromised T-cell activation and impaired downstream responses against ASFV.
