Coxsackievirus A16 induced neurological disorders in young gerbils which could serve as a new animal model for vaccine evaluation

Sun, Yisheng; Xia, Yong; Fang, Xu; Wang, Weiwei; Yang, Zhangnv; Lu, Hang-Jing; Chen, Zhiping; Miao, Ziping; Liang, Weifeng; Xu, Zhiyao; Dong, Hongjun; Qiu, Danhong; Zhang, Zhu; Veen, Stijn van der; Qian, Jie; Zhou, Bin; Yao, Pingping; Zhu, Han-Ping

doi:10.1038/srep34299

Cited by 22 publications

(22 citation statements)

References 41 publications

(60 reference statements)

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“…This is one of the biggest advantages of our model because it is clear that virus adaptation introduces a considerable number of nucleotide variations in viral genome that may dramatically alter the course of natural infection [35, 69]. Despite the variety of geographical sources for EV-D68, the strains detected in recent years have similar VP1 sequences as long as they belong to the same genetic clade [33].…”

Section: Discussionmentioning

confidence: 99%

Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus)

et al. 2016

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In recent years, there has been a significant increase in detection of Enterovirus D-68 (EV-D68) among patients with severe respiratory infections worldwide. EV-D68 is now recognized as a re-emerging pathogen; however, due to lack of a permissive animal model for EV-D68, a comprehensive understanding of the pathogenesis and immune response against EV-D68 has been hampered. Recently, it was shown that EV-D68 has a strong affinity for α2,6-linked sialic acids (SAs) and we have shown previously that α2,6-linked SAs are abundantly present in the respiratory tract of cotton rats (Sigmodon hispidus). Thus, we hypothesized that cotton rats could be a potential model for EV-D68 infection. Here, we evaluated the ability of two recently isolated EV-D68 strains (VANBT/1 and MO/14/49), along with the historical prototype Fermon strain (ATCC), to infect cotton rats. We found that cotton rats are permissive to EV-D68 infection without virus adaptation. The different strains of EV-D68 showed variable infection profiles and the ability to produce neutralizing antibody (NA) upon intranasal infection or intramuscular immunization. Infection with the VANBT/1 resulted in significant induction of pulmonary cytokine gene expression and lung pathology. Intramuscular immunization with live VANBT/1 or MO/14/49 induced strong homologous antibody responses, but a moderate heterologous NA response. We showed that passive prophylactic administration of serum with high content of NA against VANBT/1 resulted in an efficient antiviral therapy. VANBT/1-immunized animals showed complete protection from VANBT/1 challenge, but induced strong pulmonary Th1 and Th2 cytokine responses and enhanced lung pathology, indicating the generation of exacerbated immune response by immunization. In conclusion, our data illustrate that the cotton rat is a powerful animal model that provides an experimental platform to investigate pathogenesis, immune response, anti-viral therapies and vaccines against EV-D68 infection.

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Section: Discussionmentioning

confidence: 99%

Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus)

et al. 2016

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“…Sun et al. (). It was found that immune cells from Acomys , gerbils and xid mice, but not from Mus controls, failed to respond to specific thymus‐independent type 2 (TI‐2) antigens and that Acomys , gerbils and xid mice lack a subset of B lymphocytes present in normal mice (Pennello et al., ).…”

Section: Inflammation and Immunity In Regeneration Within Mammalian Smentioning

confidence: 99%

“…The regeneration capacity of gerbils appears untested, but immune deficiencies rendering these rodents much more susceptible than mice or rats to various viral, bacterial, and parasitic infections make them an important model of many human diseases, e.g. Sun et al (2016). It was found that immune cells from Acomys, gerbils and xid mice, but not from…”

Section: Mus Acomysmentioning

confidence: 99%

Macrophages and fibroblasts during inflammation and tissue repair in models of organ regeneration

2017

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This review provides a concise summary of the changing phenotypes of macrophages and fibroblastic cells during the local inflammatory response, the onset of tissue repair, and the resolution of inflammation which follow injury to an organ. Both cell populations respond directly to damage and present coordinated sequences of activation states which determine the reparative outcome, ranging from true regeneration of the organ to fibrosis and variable functional deficits. Recent work with mammalian models of organ regeneration, including regeneration of full‐thickness skin, hair follicles, ear punch tissues, and digit tips, is summarized and the roles of local immune cells in these systems are discussed. New investigations of the early phase of amphibian limb and tail regeneration, including the effects of pro‐inflammatory and anti‐inflammatory agents, are then briefly discussed, focusing on the transition from the normally covert inflammatory response to the initiation of the regeneration blastema by migrating fibroblasts and the expression of genes for limb patterning.

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“…HFMD courses are usually mild or self-limited, but a few patients could have severe symptoms or even die. In recent years, there have been several outbreaks in the West Pacific region, such as in China, Japan, Thailand, and so on [1][2][3]. There are also many HFMD case reports in Europe, such as in France and Denmark [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…The gerbil has been a suitable animal model for medical use for more than 40 years, especially for cerebral infarction. Our team established a gerbil animal model for infection with both the EV71 and CVA16 viruses successfully [2,3]. The gerbil model is more sensitive to the EV71 and CVA16 viruses than the mouse model.…”

Section: Introductionmentioning

confidence: 99%

Global Gene Expression Analysis of the Brainstem in EV71- and CVA16-Infected Gerbils

Sun

Yang

Fang

et al. 2019

Viruses

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Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the two most important pathogens of hand, foot, and mouth disease (HFMD). However, the neuropathogenesis of EV71 and CVA16 has not been elucidated. In our previous study, we established gerbils as a useful model for both EV71 and CVA16 infection. In this work, we used RNA-seq technology to analyze the global gene expression of the brainstem of EV71- and CVA16-infected gerbils. We found that 3434 genes were upregulated while 916 genes were downregulated in EV71-infected gerbils. In CVA16-infected gerbils, 1039 genes were upregulated, and 299 genes were downregulated. We also found significant dysregulation of cytokines, such as IP-10 and CXCL9, in the brainstem of gerbils. The expression levels of 10 of the most upregulated genes were confirmed by real-time RT-PCR, and the upregulated tendency of most genes was in accordance with the differential gene expression (DGE) results. Our work provided global gene expression analysis of virus-infected gerbils and laid a solid foundation for elucidating the neuropathogenesis mechanisms of EV71 and CVA16.

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Coxsackievirus A16 induced neurological disorders in young gerbils which could serve as a new animal model for vaccine evaluation

Cited by 22 publications

References 41 publications

Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus)

Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus)

Macrophages and fibroblasts during inflammation and tissue repair in models of organ regeneration

Global Gene Expression Analysis of the Brainstem in EV71- and CVA16-Infected Gerbils

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