Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Zagreb, Croatia.
Center of Excellence for Viral Immunology and Vaccines, CERVirVac, Zagreb, Croatia.
J Virol. 2023 Apr 27;97(4):e0035923. doi: 10.1128/jvi.00359-23. Epub 2023 Apr 5.
Mumps is a highly contagious viral disease that can be prevented by vaccination. In the last decade, we have encountered repeated outbreaks of mumps in highly vaccinated populations, which call into question the effectiveness of available vaccines. Animal models are crucial for understanding virus-host interactions, and viruses such as mumps virus (MuV), whose only natural host is the human, pose a particular challenge. In our study, we examined the interaction between MuV and the guinea pig. Our results present the first evidence that guinea pigs of the Hartley strain can be infected after intranasal and intratesticular inoculation. We observed a significant viral replication in infected tissues up to 5 days following infection and induction of cellular and humoral immune responses as well as histopathological changes in infected lungs and testicles, without clinical signs of disease. Transmission of the infection through direct contact between animals was not possible. Our results demonstrate that guinea pigs and guinea pig primary cell cultures represent a promising model for immunological and pathogenetic studies of the complex MuV infection. Understanding of mumps virus (MuV) pathogenesis and the immune responses against MuV infection is limited. One of the reasons is the lack of relevant animal models. This study explores the interaction between MuV and the guinea pig. We demonstrated that all tested guinea pig tissue homogenates and primary cell cultures are highly susceptible to MuV infection and that α2,3-sialylated glycans (MuV cellular receptors) are being abundantly expressed at their surface. The virus remains in the guinea pig lungs and trachea for up to 4 days following intranasal infection. Although asymptomatic, MuV infection strongly activates both humoral and cellular immune response in infected animals and provides protection against virus challenge. Infection of the lungs and testicles after intranasal and intratesticular inoculation, respectively, is also supported by histopathological changes in these organs. Our findings give perspective for application of guinea pigs in research on MuV pathogenesis, antiviral response, and vaccine development and testing.
流行性腮腺炎是一种高度传染性的病毒性疾病，可以通过接种疫苗来预防。在过去的十年中，我们在高度接种疫苗的人群中反复遇到流行性腮腺炎的爆发，这使得人们对现有疫苗的有效性产生了质疑。动物模型对于了解病毒-宿主相互作用至关重要，而像腮腺炎病毒（MuV）这样的病毒，其唯一的天然宿主是人类，这给研究带来了特殊的挑战。在我们的研究中，我们研究了 MuV 与豚鼠的相互作用。我们的研究结果首次证明，经鼻腔和睾丸内接种后，豚鼠可感染 Hartley 株 MuV。我们观察到，在感染后 5 天内，受感染组织中的病毒复制显著，并且诱导了细胞和体液免疫反应，以及感染肺部和睾丸的组织病理学变化，但没有疾病的临床迹象。动物之间的直接接触不能传播感染。我们的结果表明，豚鼠和豚鼠原代细胞培养物是研究复杂的 MuV 感染的免疫和发病机制的有前途的模型。对腮腺炎病毒（MuV）发病机制和针对 MuV 感染的免疫反应的了解有限。其中一个原因是缺乏相关的动物模型。本研究探讨了 MuV 与豚鼠的相互作用。我们证明，所有测试的豚鼠组织匀浆和原代细胞培养物均高度易感 MuV 感染，并且其表面大量表达α2,3-唾液酸化聚糖（MuV 细胞受体）。在鼻腔感染后，病毒仍在豚鼠的肺部和气管中存在长达 4 天。尽管无症状，但 MuV 感染强烈激活了感染动物的体液和细胞免疫反应，并为病毒攻击提供了保护。鼻腔和睾丸内接种后，肺部和睾丸感染也分别通过这些器官的组织病理学变化得到支持。我们的研究结果为豚鼠在 MuV 发病机制、抗病毒反应、疫苗开发和测试方面的应用提供了前景。
