A mouse model and pathogenesis study for CVA19 first isolated from hand, foot, and mouth disease.
A mouse model and pathogenesis study for CVA19 first isolated from hand, foot, and mouth disease.
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DOI：
10.1080/22221751.2023.2177084
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发表时间：
2023-12
影响因子：
13.2
通讯作者：
中科院分区：
文献类型：
--
作者：
柯萨奇病毒A19(CoxsackieVirus A19，CVA19)是肠道病毒(EV)C组的成员。最近，我们首次报道了一例CVA19感染的手足口病(HFMD)病例。然而，由于缺乏合适的动物模型，目前对CVA19感染，特别是脑脊髓炎和腹泻的发病机制的认识仍然非常有限。在此，我们以7日龄ICR小鼠为研究对象，成功建立了CVA19小鼠模型。我们的结果发现，该病毒株可直接感染神经元、脑星形胶质细胞和脊髓运动神经元，导致神经并发症，如急性迟缓性瘫痪。重要的是，从受感染小鼠的脊髓中分离出的病毒在哺乳小鼠中引起了严重的疾病，在一定程度上满足了科赫的假设。CVA19感染导致腹泻，典型的病理特征为肠绒毛缩短，分泌细胞和凋亡细胞增多，炎性细胞浸润。CVA19感染小鼠血清细胞因子浓度明显升高，外周血炎性细胞增多，提示CVA19感染可引起全身炎症反应。最后，我们发现病毒唑和CVA19VP1单抗不能阻止疾病的进展，但较高浓度的抗血清和干扰素-α2可以对CVA19起到保护作用。综上所述，本研究表明，一株天然的小鼠适应的CVA19毒株通过口腔感染导致小鼠腹泻和脑脊髓炎，这为研究CVA19的发病机制以及评估疫苗和抗病毒药物的效果提供了有用的工具。
Coxsackievirus A19 (CVA19) is a member of Enterovirus (EV) C group in the Picornaviridae family. Recently, we reported a case of CVA19-infected hand, foot, and mouth disease (HFMD) for the first time. However, the current body of knowledge on the CVA19 infection, particularly the pathogenesis of encephalomyelitis and diarrhoea is still very limited, due to the lack of suitable animal models. Here, we successfully established a CVA19 mouse model via oral route based on 7-day-old ICR mice. Our results found the virus strain could directly infect the neurons, astrocytes of brain, and motor neurons of spinal cord causing neurological complications, such as acute flaccid paralysis. Importantly, viruses isolated from the spinal cords of infected mice caused severe illness in suckling mice, fulfilling Koch’s postulates to some extent. CVA19 infection led to diarrhoea with typical pathological features of shortened intestinal villi, increased number of secretory cells and apoptotic intestinal cells, and inflammatory cell infiltration. Much higher concentrations of serum cytokines and more peripheral blood inflammatory cells in CVA19-infected mice indicated a systematic inflammatory response induced by CVA19 infection. Finally, we found ribavirin and CVA19 VP1 monoclonal antibody could not prevent the disease progression, but higher concentrations of antisera and interferon alpha 2 (IFN-α2) could provide protective effects against CVA19. In conclusion, this study shows that a natural mouse-adapted CVA19 strain leads to diarrhoea and encephalomyelitis in a mouse model via oral infection, which provides a useful tool for studying CVA19 pathogenesis and evaluating the efficacy of vaccines and antivirals.
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影响因子：
5.6
作者：
Ji W;Hu Q;Zhang M;Zhang C;Chen C;Yan Y;Zhang X;Chen S;Tao L;Zhang W;Jin Y;Duan G
通讯作者：
Duan G
影响因子：
13.2
作者：
通讯作者：
--
影响因子：
3.7
作者：
Chansaenroj J;Tuanthap S;Thanusuwannasak T;Duang-In A;Klinfueng S;Thaneskongtong N;Vutithanachot V;Vongpunsawad S;Poovorawan Y
通讯作者：
Poovorawan Y
影响因子：
11.8
作者：
Huang J;Liao Q;Ooi MH;Cowling BJ;Chang Z;Wu P;Liu F;Li Y;Luo L;Yu S;Yu H;Wei S
通讯作者：
Wei S
影响因子：
3
作者：
Donbraye, Emmanuel;Olasunkanmi, Oluwatayo Israel;Adeniji, Johnson Adekunle
通讯作者：
Adeniji, Johnson Adekunle