College of Animal Sciences, Key Lab for Zoonoses Research, Ministry of Education, Jilin University, 5333 Xi'an Road, Changchun 130062, China.
Int J Mol Sci. 2022 Apr 19;23(9):4479. doi: 10.3390/ijms23094479.
Porcine circovirus 2 (PCV2) and pseudorabies virus (PRV) are two important pathogens in the pig industry. PCV2 or PRV infection can induce endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). However, the effect of PCV2 and PRV coinfection on the ERS and UPR pathways remains unclear. In this study, we found that PRV inhibited the proliferation of PCV2 mainly at 36 to 72 hpi, while PCV2 enhanced the proliferation of PRV in the middle stage of the infection. Notably, PRV is the main factor during coinfection. The results of the transcriptomic analysis showed that coinfection with PCV2 and PRV activated cellular ERS, and upregulated expressions of the ERS pathway-related proteins, including GRP78, eIF2α, and ATF4. Further research indicated that PRV played a dominant role in the sequential infection and coinfection of PCV2 and PRV. PCV2 and PRV coinfection induced the ERS activation via the PERK-eIF2α-ATF4-CHOP axis and IRE1-XBP1-EDEM pathway, and thus may enhance cell apoptosis and exacerbate the diseases.
猪圆环病毒 2 型（PCV2）和猪伪狂犬病病毒（PRV）是猪产业中的两种重要病原体。PCV2 或 PRV 感染可诱导内质网应激（ERS）和未折叠蛋白反应（UPR）。然而，PCV2 和 PRV 混合感染对 ERS 和 UPR 途径的影响尚不清楚。在本研究中，我们发现 PRV 主要在 36 至 72 小时感染时抑制 PCV2 的增殖，而 PCV2 在感染的中期增强了 PRV 的增殖。值得注意的是，PRV 是混合感染过程中的主要因素。转录组分析的结果表明，PCV2 和 PRV 的混合感染激活了细胞 ERS，并上调了 ERS 途径相关蛋白的表达，包括 GRP78、eIF2α 和 ATF4。进一步的研究表明，PRV 在 PCV2 和 PRV 的顺序感染和混合感染中起主导作用。PCV2 和 PRV 的混合感染通过 PERK-eIF2α-ATF4-CHOP 轴和 IRE1-XBP1-EDEM 途径诱导 ERS 激活，从而可能增强细胞凋亡并加重疾病。
