Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, P.R. China.
Virulence. 2021 Dec;12(1):1011-1021. doi: 10.1080/21505594.2021.1908742.
Porcine deltacoronavirus (PDCoV) is a potentially emerging zoonotic pathogen that causes severe diarrhea in young pigs, with a risk of fatal dehydration. Its pathogenicity on neonatal piglet has been previously reported, however, it is less known if the coinfection with immunosuppressive pathogens can influence PDCoV disease manifestation. Here, a coinfection model of PDCoV and porcine reproductive and respiratory syndrome virus (PRRSV), a global-spread immunosuppressive virus, was set to study their interaction. Weaning pigs in the coinfection group were intranasally inoculated with PRRSV NADC30-like virus and latterly orally inoculated with PDCoV at three day-post-inoculation (DPI). Unexpectedly, compared with pigs in the PDCoV single-infected group, the coinfected pigs did not show any obvious diarrhea, as PDCoV fecal shedding, average daily weight gain (ADWG), gross and microscopic lesions and PDCoV IHC scores consistently indicated that PRRSV coinfection lessened PDCoV caused diarrhea. Additionally, three proinflammatory cytokines TNF-α, IL-1 and IL-6, which can be secreted by PRRSV infected macrophages, were detected to be highly expressed at the intestine from both PRRSV infected groups. By adding to PDCoV-infected cells, these three cytokines were further confirmed to be able to inhibit the PDCoV replication post its cellular entry. Meanwhile, the inhibition effect of the supernatant from PRRSV-infected PAMs could be obviously blocked by the antagonist of these three cytokines. In conclusion, PRRSV coinfection increased TNF-α, IL-1, and IL-6 in the microenvironment of intestines, which inhibits the PDCoV proliferation, leading to lessened severity of diarrhea. The findings provide some new insight into the pathogenesis and replication regulation of PDCoV.
猪德尔塔冠状病毒（PDCoV）是一种具有潜在新兴性的人畜共患病病原体，可导致仔猪严重腹泻，有致命性脱水的风险。其对新生仔猪的致病性此前已有报道，但尚不清楚免疫抑制性病原体的合并感染是否会影响 PDCoV 疾病表现。在这里，我们建立了 PDCoV 和猪繁殖与呼吸综合征病毒（PRRSV）的合并感染模型，后者是一种全球性传播的免疫抑制病毒，以研究它们之间的相互作用。在合并感染组中，断奶仔猪经鼻腔接种 NADC30 样 PRRSV 病毒，随后在接种后第 3 天经口接种 PDCoV。出乎意料的是，与 PDCoV 单一感染组的猪相比，合并感染组的猪没有出现明显的腹泻，因为 PDCoV 粪便脱落、平均日增重（ADWG）、大体和显微镜病变以及 PDCoV IHC 评分均表明 PRRSV 合并感染减轻了 PDCoV 引起的腹泻。此外，三种促炎细胞因子 TNF-α、IL-1 和 IL-6，它们可以由 PRRSV 感染的巨噬细胞分泌，在 PRRSV 感染组的肠道中均高度表达。将这三种细胞因子添加到 PDCoV 感染的细胞中，进一步证实它们可以在 PDCoV 进入细胞后抑制其复制。同时，PRRSV 感染的 PAMs 上清液的抑制作用可以被这三种细胞因子的拮抗剂明显阻断。总之，PRRSV 合并感染增加了肠道微环境中 TNF-α、IL-1 和 IL-6 的表达，抑制了 PDCoV 的增殖，从而减轻了腹泻的严重程度。这些发现为 PDCoV 的发病机制和复制调控提供了一些新的见解。
