Apoptosis versus survival of African horse sickness virus serotype 4-infected horse peripheral blood mononuclear cells

Abstract

Expanding on our previous work, this study used transcriptome analysis of RNA sequences to investigate the various factors that contributed to either inducing apoptosis that resulted in cell death or promoting the survival of African horse sickness virus serotype 4 (AHSV4)-infected horse peripheral blood mononuclear cells (PBMC) after 24 h. Apoptosis is a host defense mechanism that prevents virus replication, accumulation and spread of progeny viruses. AHSV4-infected PBMC were killed via the intrinsic and the perforin/granzyme pathways of apoptosis during the attenuated AHSV4 (attAHSV4) in vivo primary and secondary immune responses. Trained innate immunity played an important role in circumventing viral interference that resulted in the elimination of AHSV4-infected PBMC through the intrinsic and the extrinsic pathways of apoptosis during the virulent AHSV4 (virAHSV4) in vitro secondary immune response. Oxidative stress in conjunction with IRE1α pro-apoptotic signaling played a major role in the induction of the intrinsic pathway of apoptosis and cytotoxic lymphocytes induced the perforin/granzyme or extrinsic pathways of apoptosis. In contrast, AHSV4-infected PBMC survived during the virAHSV4 in vitro primary immune response, which allows unrestrained viral replication. The virAHSV4 interference with the innate immune response resulted in impaired NK cell responses and delayed immune responses, which together with the antioxidant defense system promoted AHSV4-infected PBMC survival.