The replicative success of vaccinia virus (VACV) depends on its ability to subvert host functions. Poxviruses multiplication and maturation are closely associated with the endoplasmic reticulum (ER) and its membranes. This organelle responds to disturbances caused by the accumulation of misfolded proteins, leading to processing of these proteins or even programmed cell death through the unfolded protein response (UPR). Several studies show that different viruses can activate UPR pathway components and negatively modulate others. Here, we investigate the effects of infections by zoonotic VACV strains from Brazil, Guarani P1 virus (GP1V) and Passatempo virus (PSTV), in the activation of UPR pathway sensors. We observed translocation of ATF6 to the nucleus as well as transcriptional increase after GP1V, PSTV, and reference strain Western Reserve (WR) infection. XBP1 processing appears to be negatively modulated after VACV infection; however, inhibition of the inositol-requiring enzyme 1 (IRE1) kinase domain led to a reduction in plaque sizes for these viruses. The absence of PKR-like endoplasmic reticulum kinase (PERK) has an impact on the plaque phenotype of GP1V, PSTV viruses, as well as for the prototypical strain WR. These results indicate that the VACV manipulates the three arms of the UPR path differently to ensure replicative success.
Keywords: Guarani P1 virus; Passatempo virus; WR virus; Zoonotic poxvirus; unfolded protein response; vaccinia virus.