College of Veterinary Medicine, Jilin University, Changchun, China.
Key laboratory for Zoonosis, Ministry of Education, Institute of Zoonosis of the Jilin University, Changchun, China.
PLoS One. 2018 Feb 15;13(2):e0193155. doi: 10.1371/journal.pone.0193155. eCollection 2018.
HY12 viruses are enteroviruses recently isolated from cattle characterized by severe respiratory and digestive disease with high morbidity and mortality in China. While the viruses exhibit unique biological and molecular characters distinct from known enterovirus E, the pathogenicity and viral pathogenesis remains largely unknown.
Neonatal mice of Balb/C, ICR, and Kunming strain are infected with HY12 to determine the susceptible mouse strain. The minimal infection dose, the virus infection routes, the pathogenicity and tissue tropism for HY12 were determined by infecting susceptible mice with HY12 viruses, and confirmed by different approaches including virus isolation and recovery, virus detection, histopathology, and immunohistochemistry.
A murine model for HY12 infection was successfully established and employed to investigate the pathogenicity of HY12 viruses. ICR mouse strain is the most susceptible strain for HY12 infection with a minimal infective dose as 2×106TCID50/mouse. HY12 viruses have the capability of infecting ICR suckling mice via all infection routes including intranasal administration, oral administration, intraperitoneal injection, subcutaneous injection, and intramuscular injection, which are confirmed by the isolation and recovery of viruses from HY12-infected mice; detection of viruses by RT-PCR; observations of pathological lesions and inflammatory cell infiltrations in the intestine, lung, liver, and brain; uncovering of HY12 virus antigens in majority of tissues, especially in intestine, lung, and infected brain of mice by immunohistochemistry assay.
A neonatal murine model for HY12 infection is successfully established for determining the susceptible mouse strain, the minimal infective dose, the infection route, the viral pathogenicity and the tropism of HY12, thus providing an invaluable model system for elucidating the pathogenesis of HY12 viruses and the elicited immunity.
HY12 病毒是最近从中国牛群中分离出来的肠道病毒，具有严重的呼吸和消化疾病，发病率和死亡率很高。虽然这些病毒表现出独特的生物学和分子特征，与已知的肠道病毒 E 不同，但它们的致病性和病毒发病机制在很大程度上仍然未知。
用 HY12 感染新生的 Balb/C、ICR 和昆明品系小鼠，确定易感小鼠品系。通过用 HY12 病毒感染易感小鼠，确定 HY12 的最小感染剂量、病毒感染途径、致病性和组织嗜性，并通过病毒分离和恢复、病毒检测、组织病理学和免疫组织化学等不同方法进行确认。
成功建立了 HY12 感染的小鼠模型，并用于研究 HY12 病毒的致病性。ICR 小鼠是 HY12 感染最易感的品系，最小感染剂量为 2×106TCID50/只。HY12 病毒能够通过所有感染途径感染 ICR 乳鼠，包括鼻腔内给药、口服给药、腹腔内注射、皮下注射和肌肉内注射，这通过从 HY12 感染的小鼠中分离和恢复病毒、通过 RT-PCR 检测病毒、观察肠道、肺、肝和脑的病理损伤和炎症细胞浸润、通过免疫组织化学检测 HY12 病毒抗原在大多数组织中的表达，特别是在感染小鼠的肠道、肺和感染的脑组织中，得到了证实。
成功建立了 HY12 感染的新生小鼠模型，用于确定易感小鼠品系、最小感染剂量、感染途径、HY12 的病毒致病性和嗜性，为阐明 HY12 病毒的发病机制和激发的免疫提供了一个非常有价值的模型系统。
