Low-Concentration T-2 Toxin Attenuates Pseudorabies Virus Replication in Porcine Kidney 15 Cells.

Kuankuan Xiong,Yi Hu,Yingxin Wu,Siliang Yi,Lei Tan,Lingchen Yang,Aibing Wang

doi:10.3390/toxins14020121

Abstract

Pseudorabies, caused by pseudorabies virus (PRV), is the main highly infectious disease that severely affects the pig industry globally. T-2 toxin (T2), a significant mycotoxin, is widely spread in food and feeds and shows high toxicity to mammals. The potential mechanism of the interaction between viruses and toxins is of great research value because revealing this mechanism may provide new ideas for their joint prevention and control. In this study, we investigated the effect of T2 on PRV replication and the mechanism of action. The results showed that at a low dose (10 nM), T2 had no significant effect on porcine kidney 15 (PK15) cell viability. However, this T2 concentration alleviated PRV-induced cell injury and increased cell survival time. Additionally, the number of PK15 cells infected with PRV significantly reduced by T2 treatment. Similarly, T2 significantly decreased the copy number of PRV. Investigation of the mechanism revealed that 10 nM T2 significantly inhibits PRV replication and leads to downregulation of oxidative stress- and apoptosis-related genes. These results suggest that oxidative stress and apoptosis are involved in the inhibition of PRV replication in PK15 cells by low-concentration T2. Taken together, we demonstrated the protective effects of T2 against PRV infection. A low T2 concentration inhibited the replication of PRV in PK15 cells, and this process was accompanied by downregulation of the oxidative stress and apoptosis signaling pathways. Our findings partly explain the interaction mechanism between T2 and PRV, relating to oxidative stress and apoptosis, though further research is required.

Highlights

Pseudorabies virus (PRV), called Suid herpesvirus 1, is an enveloped, doublestranded linear DNA virus belonging to the subfamily Alphaherpesvirinae, within the Herpesviridae family [1]
To verify that oxidative stress and apoptosis are involved in the inhibition of PRV replication in porcine kidney 15 (PK15) cells by low-concentration T2, we examined the protein expression of cleaved-caspase-3, cleaved-caspase-8, Bax, Bcl-2, Nrf2, and GPx-1 by Western blotting
Our finding is similar to the result that the vomiting toxin DON significantly reduces the replication of porcine reproductive and respiratory syndrome virus (PRRSV) in vitro and in vivo [19]. Because both T2 and PRV induce oxidative stress damage accompanied by apoptosis, we investigated whether the T2 inhibition of PRV replication is related to oxidative stress and apoptosis by determining the expression level of cytokines related to oxidative stress and apoptosis

Summary

Introduction

Pseudorabies virus (PRV), called Suid herpesvirus 1, is an enveloped, doublestranded linear DNA virus belonging to the subfamily Alphaherpesvirinae, within the Herpesviridae family [1]. PRV can infect a wide variety of animals, including pigs, ruminants (sheep/goat and cattle/cows), carnivores (minks and foxes), and rodents, though pigs, including wild boars, are the natural host for this pathogen [2]. A live PRV strain was successfully isolated from a patient with acute encephalitis, and its potential cross-species transmission ability has drawn wide attention [3]. PRV infects porcine kidney 15 (PK15) cells and causes cytopathy and cell damage. The virus infection causes oxidative stress, affects the activity of antioxidant enzymes, and induces the generation of reactive oxygen species (ROS), further damaging cell components and even leading to cell death [5]. PRV-induced oxidative stress activates Bcl-2-family-and caspase-family-related proteins, further leading to apoptosis and DNA damage [6]

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Conclusion