MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.
J Virol. 2022 Jul 27;96(14):e0047722. doi: 10.1128/jvi.00477-22. Epub 2022 Jun 27.
The mechanisms of colostrum-mediated virus transmission are difficult to elucidate because of the absence of experimental animal models and the difficulties in tissue sample collection from mothers in the peripartum period. Porcine epidemic diarrhea virus (PEDV) is a reemerging enteropathogenic coronavirus that has catastrophic impacts on the global pig industry. PEDV primarily infects neonatal piglets by multiple routes, especially 1- to 2-day-old neonatal piglets. Here, our epidemiological investigation and animal challenge experiments revealed that PEDV could be vertically transmitted from sows to neonatal piglets via colostrum, and CD3 T cells in the colostrum play an important role in this process. The results showed that PEDV colonizing the intestinal epithelial cells (IECs) of orally immunized infected sows could be transferred to CD3 T cells located just beneath the IECs. Next, PEDV-carrying CD3 T cells, with the expression of integrin α4β7 and CCR10, migrate from the intestine to the mammary gland through blood circulation. Arriving in the mammary gland, PEDV-carrying CD3 T cells could be transported across mammary epithelial cells (MECs) into the lumen (colostrum), as illustrated by an autotransfusion assay and an MECs/T coculture system. The PEDV-carrying CD3 T cells in colostrum could be interspersed between IECs of neonatal piglets, causing intestinal infection via cell-to-cell contact. Our study demonstrates for the first time that colostrum-derived CD3 T cells comprise a potential route for the vertical transmission of PEDV. The colostrum represents an important infection route for many viruses. Here, we demonstrate the vertical transmission of porcine epidemic diarrhea virus (PEDV) from sows to neonatal piglets via colostrum. PEDV colonizing the intestinal epithelial cells could transfer the virus to CD3 T cells located in the sow intestine. The PEDV-carrying CD3 T cells in the sow intestine, with the expression of integrin α4β7 and CCR10, arrive at the mammary gland through blood circulation and are transported across mammary epithelial cells into the lumen, finally leading to intestinal infection via cell-to-cell contact in neonatal piglets. Our study not only demonstrates an alternative route of PEDV infection but also provides an animal model of vertical transmission of human infectious disease.
初乳介导的病毒传播机制难以阐明，因为缺乏实验动物模型，且难以在围产期从母亲身上采集组织样本。猪流行性腹泻病毒（PEDV）是一种重新出现的肠致病性冠状病毒，对全球养猪业造成了灾难性的影响。PEDV 主要通过多种途径感染新生仔猪，尤其是 1-2 日龄的新生仔猪。在这里，我们的流行病学调查和动物挑战实验表明，PEDV 可以通过初乳从母猪垂直传播给新生仔猪，初乳中的 CD3 T 细胞在这个过程中起着重要作用。结果表明，定植于经口免疫感染母猪肠道上皮细胞（IECs）的 PEDV 可转移至位于 IECs 下方的 CD3 T 细胞。接下来，PEDV 携带的 CD3 T 细胞通过血液循环从肠道迁移到乳腺，这些细胞表达整合素 α4β7 和 CCR10。到达乳腺后，PEDV 携带的 CD3 T 细胞可通过血乳屏障进入乳腔（初乳），这一过程可通过自身输血试验和 MECs/T 共培养系统来证明。在初乳中，PEDV 携带的 CD3 T 细胞可散布在新生仔猪的 IEC 之间，通过细胞间接触引起肠道感染。我们的研究首次证明，初乳衍生的 CD3 T 细胞是 PEDV 垂直传播的潜在途径。初乳是许多病毒的重要感染途径。在这里，我们证明了 PEDV 可通过初乳从母猪垂直传播给新生仔猪。定植于肠道上皮细胞的 PEDV 可将病毒转移至位于母猪肠道中的 CD3 T 细胞。PEDV 携带的 CD3 T 细胞在带有整合素 α4β7 和 CCR10 表达的母猪肠道中，通过血液循环到达乳腺，并通过血乳屏障转运至乳腔，最终通过细胞间接触在新生仔猪中引起肠道感染。我们的研究不仅证明了 PEDV 感染的另一种途径，还提供了一种人类传染病垂直传播的动物模型。
