Laboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
Polymer Chemistry & Biomaterials Group, Centre of Macromolecular Chemistry, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281, 9000, Ghent, Belgium.
Vet Res. 2024 Sep 20;55(1):113. doi: 10.1186/s13567-024-01374-y.
Transmissible gastroenteritis virus (TGEV) causes high mortality in young piglets (< 3 days of age). With aging, the susceptibility/morbidity/mortality rates drop. We previously hypothesized that the age-related changes in the intestinal mucus could be responsible for this resistance. Hence, this study investigated the effect of porcine intestinal mucus from 3-day and 3-week-old pigs on the free mobility of the virulent TGEV Miller strain, and on the infection in swine testicle (ST) cells. Single particle tracking (SPT) revealed that TGEV had significantly higher diffusion coefficients in 3-day mucus compared to 3-week mucus. TGEV and charged and uncharged control nanoparticles diffused freely in 3-day mucus but were hindered by 3-week mucus in the diffusion model; TGEV mimicked the diffusion behavior of negatively charged carboxylated particles. Inoculation of ST cells with TGEV in the presence of 3-week mucus resulted in a significantly lower average number of infected cells (30.9 ± 11.9/5 fields) compared with 3-day mucus (84.6 ± 16.4/5 fields). These results show that 3-week mucus has a significant TGEV-blocking activity compared to 3-day mucus in free diffusion and infection of the underlying susceptible cells. Additionally, a label-free proteomics analysis revealed an increased expression of mucin 13, known for negatively regulating the tight junctions in intestinal epithelium, in 3-day-old pigs. In 3-week-old pigs, a higher expression of mucin 2, a type of secreted mucin which is known for inhibiting coronavirus infection, was observed. Concludingly, this study demonstrated a protective effect of 3-week mucus against viral infections.
传染性胃肠炎病毒（TGEV）可导致仔猪（<3 日龄）死亡率升高。随着年龄的增长，易感性/发病率/死亡率下降。我们之前假设，肠道黏液的年龄相关变化可能是导致这种抵抗力的原因。因此，本研究探讨了来自 3 日龄和 3 周龄猪的猪肠黏液对强毒 TGEV Miller 株的自由迁移能力以及对猪睾丸（ST）细胞感染的影响。单颗粒跟踪（SPT）显示，与 3 周龄黏液相比，TGEV 在 3 日龄黏液中的扩散系数明显更高。TGEV 和带电荷及不带电荷的对照纳米颗粒在 3 日龄黏液中自由扩散，但在扩散模型中受到 3 周龄黏液的阻碍；TGEV 模拟了带负电荷的羧化颗粒的扩散行为。在 3 周龄黏液存在的情况下，将 TGEV 接种到 ST 细胞中，与 3 日龄黏液（84.6 ± 16.4/5 个视野）相比，感染细胞的平均数量显著减少（30.9 ± 11.9/5 个视野）。这些结果表明，与 3 日龄黏液相比，3 周龄黏液在自由扩散和感染潜在易感细胞方面对 TGEV 具有显著的阻断活性。此外，无标记蛋白质组学分析显示，在 3 日龄猪中，黏蛋白 13 的表达增加，黏蛋白 13 已知可负调控肠道上皮细胞的紧密连接。在 3 周龄猪中，观察到黏蛋白 2的表达增加，黏蛋白 2 是一种已知可抑制冠状病毒感染的分泌型黏蛋白。总之，本研究表明 3 周龄黏液对病毒感染具有保护作用。
