Del Sorbo Luca, Cerracchio Claudia, Serra Francesco, Canzanella Silvia, Giugliano Rosa, Lambiase Sara, Aránguiz Nicolás Pizarro, Esposito Mauro, Amoroso Maria Grazia, Fusco Giovanna, Fiorito Filomena
Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137, Naples, Italy.
Istituto Zooprofilattico del Mezzogiorno, Portici, 80055, Naples, Italy.
Arch Toxicol. 2025 May;99(5):2211-2223. doi: 10.1007/s00204-025-03981-w. Epub 2025 Feb 22.
In humans as well as in animals, the toxic contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) stimulates immunosuppression and increases responsiveness to infectious diseases. The relationship between environmental contaminants and different infectious diseases, including COVID-19, has been described. Nevertheless, reports about the potential impact of TCDD on coronaviruses (CoVs) are limited. In this study, the impact of TCDD (0-100 pg/mL) was assessed during infection in vitro with canine coronavirus (CCoV-II), the alphaCoV causing moderate enteric disease in dogs, although genetic alterations may surprisingly generate new dangerous strains. For instance, outbreaks of lethal infections in dogs were related to highly virulent CCoV strains, and cases of pneumonia and malaise in humans were associated with new canine-feline recombinant strains of CCoV, underlining the cross-species spread capability of CoVs. Herein, during CCoV infection, TCDD induced a substantial growth in virus yield and in the expression of viral nucleocapsid protein in infected groups. Infected cells exhibited alterations in cell morphology, extensively enhanced by TCDD. Moreover, in infection, TCDD modulated the protein levels of aryl hydrocarbon receptor (AHR), a signaling responsive to both environmental contaminant and CoVs infections. Overall, our findings showed that TCDD, playing a role in AHR signaling, may worsen CCoV infection.
在人类和动物中，有毒污染物2,3,7,8-四氯二苯并对二恶英（TCDD）会刺激免疫抑制并增加对传染病的易感性。环境污染物与包括COVID-19在内的不同传染病之间的关系已有描述。然而，关于TCDD对冠状病毒（CoV）潜在影响的报道有限。在本研究中，评估了TCDD（0-100 pg/mL）在体外感染犬冠状病毒（CCoV-II）期间的影响，CCoV-II是一种引起犬类中度肠道疾病的α冠状病毒，尽管基因改变可能会意外产生新的危险毒株。例如，犬类致命感染的爆发与高毒力的CCoV毒株有关，人类的肺炎和不适病例与新的犬猫重组CCoV毒株有关，这突出了CoV的跨物种传播能力。在此，在CCoV感染期间，TCDD在感染组中诱导病毒产量和病毒核衣壳蛋白表达大幅增加。受感染细胞表现出细胞形态改变，TCDD可使其显著增强。此外，在感染过程中，TCDD调节芳烃受体（AHR）的蛋白水平，AHR是一种对环境污染物和CoV感染均有反应的信号通路。总体而言，我们的研究结果表明，在AHR信号通路中起作用的TCDD可能会加重CCoV感染。
