A hSCARB2-transgenic mouse model for Coxsackievirus A16 pathogenesis

Abstract Background Coxsackievirus A16 (CA16) is one of the neurotropic pathogen that has been associated with severe neurological forms of hand, foot, and mouth disease (HFMD), but its pathogenesis is not yet clear. The limited host range of CA16 make the establishment of a suitable animal model that can recapitulate the neurological pathology observed in human HFMD more difficult. Because the human scavenger receptor class B, member 2 (hSCARB2) is a cellular receptor for CA16, we used transgenic mice bearing human SCARB2 and nasally infected them with CA16 to study the pathogenicity of the virus. Methods Coxsackievirus A16 was administered by intranasal instillation to groups of hSCARB2 transgenic mice and clinical signs were observed. Sampled at different time-points to document and characterize the mode of viral dissemination, pathological change and immune response of CA16 infection. Results Weight loss and virus replication in lung and brain were observed in hSCARB2 mice infected with CA16, indicating that these animals could model the neural infection process. Viral antigens were observed in the alveolar epithelia and brainstem cells. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes into the alveolar interstitial in lung and diffuse punctate hemorrhages in the capillaries of the brainstem. In addition, we detected the expression levels of inflammatory cytokines and detected high levels of interleukin IL-1β, IL-6, IL-18, and IFN-γ in nasal mucosa, lungs and brain tissues. Conclusions The hSCARB2-transgenic mice can be productively infected with CA16 via respiratory route and exhibited a clear tropism to lung and brain tissues, which can serve as a model to investigate the pathogenesis of CA16 associated respiratory and neurological disease.

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A hSCARB2-transgenic mouse model for Coxsackievirus A16 pathogenesis

10.21203/rs.3.rs-86918/v1 ◽

2020 ◽

Author(s):

Yanli Chen ◽

Heng Li ◽

Jinxi Yang ◽

Huiwen Zheng ◽

Lei Guo ◽

...

Keyword(s):

Transgenic Mice ◽

Scavenger Receptor ◽

Clinical Signs ◽

Foot And Mouth Disease ◽

Infection Process ◽

Coxsackievirus A16 ◽

Class B ◽

Suitable Animal Model ◽

Neurological Pathology ◽

Brain Tissues

Abstract Background: Coxsackievirus A16 (CA16) is one of the neurotropic pathogen that has been associated with severe neurological forms of hand, foot, and mouth disease (HFMD), but its pathogenesis is not yet clear. The limited species tropism of CA16 make the establishment of a suitable animal model that can recapitulate the neurological pathology observed in human HFMD more difficult. Because the human scavenger receptor class B, member 2 (hSCARB2) is a cellular receptor for CA16, we used transgenic mice bearing human SCARB2 and nasally infected them with CA16 to study the pathogenicity of the virus.Methods: Coxsackievirus A16 was administered by intranasal instillation to groups of hSCARB2 transgenic mice and clinical signs were observed. Sampled at different time-points to document and characterize the mode of viral dissemination, pathological change and immune response of CA16 infection. Results: Weight loss and virus replication in lung and brain were observed in hSCARB2 mice infected with CA16, indicating that these animals could model the neural infection process. Viral antigens were observed in the alveolar epithelia and brainstem cells. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes into the alveolar interstitial in lung and diffuse punctate hemorrhages in the capillaries of the brainstem. In addition, we detected the expression levels of inflammatory cytokines and detected high levels of interleukin IL-1β, IL-6, IL-18, and IFN-γ in nasal mucosa, lungs and brain tissues. Conclusions: The hSCARB2-transgenic mice can be productively infected with CA16 via respiratory route and exhibited a clear tropism to lung and brain tissues, which can serve as a model to investigate the pathogenesis of CA16 associated respiratory and neurological disease.

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Effect of Plant Compound Curcumin on the Expression of SR-BI and ABCA1 in Hippocampal Neurons of APPswe/PS1dE9 Double Transgenic Mice

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.781-784.1144 ◽

2013 ◽

Vol 781-784 ◽

pp. 1144-1147

Author(s):

Jie Yun Sun ◽

Zhi Peng Teng ◽

Chen Wang ◽

Ming Yuan Tian ◽

Xiong Zhang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transgenic Mice ◽

Hippocampal Neurons ◽

Cholesterol Metabolism ◽

Scavenger Receptor ◽

Type I ◽

Atp Binding Cassette Transporter ◽

Class B ◽

Double Transgenic Mice

Disorder of cholesterol metabolism plays important roles in pathogenesis of Alzheimer’s disease (AD). Plant compound curcumin has been reported to decrease Aβ deposition and cholesterol in serum, while the detailed mechanism is still unknown. To investigate the effect of curcumin on the cholesterol metabolism in Alzheimer’s disease, APPswe/PS1dE9 double transgenic mice were fed with 500ppm of curcumin every day for six months. Immunohistochemistryresults showed that the expression of ATP-binding cassette transporter A1 (ABCA1) in hippocampal neurons was increased significantly, whereas the expression of scavenger receptor class B type I (SR-BI) was not detected. These findings suggest that curcumin may promote cholesterol efflux via ABCA1 transmembrane-transport system rather than SR-BI in neurons of AD.

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Lower Plasma Levels and Accelerated Clearance of High Density Lipoprotein (HDL) and Non-HDL Cholesterol in Scavenger Receptor Class B Type I Transgenic Mice

Journal of Biological Chemistry ◽

10.1074/jbc.274.11.7165 ◽

1999 ◽

Vol 274 (11) ◽

pp. 7165-7171 ◽

Cited By ~ 179

Author(s):

Yukihiko Ueda ◽

Lori Royer ◽

Elaine Gong ◽

Junli Zhang ◽

Philip N. Cooper ◽

...

Keyword(s):

Transgenic Mice ◽

High Density Lipoprotein ◽

Plasma Levels ◽

Scavenger Receptor ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Type I ◽

Lower Plasma ◽

Scavenger Receptor Class ◽

Class B

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Bioinformatics-based prediction of conformational epitopes for Enterovirus A71 and Coxsackievirus A16

Scientific Reports ◽

10.1038/s41598-021-84891-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Liping Wang ◽

Miao Zhu ◽

Yulu Fang ◽

Hao Rong ◽

Liuying Gao ◽

...

Keyword(s):

Foot And Mouth Disease ◽

Distribution Patterns ◽

Vital Role ◽

Coxsackievirus A16 ◽

Essential Information ◽

Site Distribution ◽

The North ◽

Conformational Epitopes ◽

Enterovirus A71 ◽

Antigenic Evolution

AbstractEnterovirus A71 (EV-A71), Coxsackievirus A16 (CV-A16) and CV-A10 are the major causative agents of hand, foot and mouth disease (HFMD). The conformational epitopes play a vital role in monitoring the antigenic evolution, predicting dominant strains and preparing vaccines. In this study, we employed a Bioinformatics-based algorithm to predict the conformational epitopes of EV-A71 and CV-A16 and compared with that of CV-A10. Prediction results revealed that the distribution patterns of conformational epitopes of EV-A71 and CV-A16 were similar to that of CV-A10 and their epitopes likewise consisted of three sites: site 1 (on the “north rim” of the canyon around the fivefold vertex), site 2 (on the “puff”) and site 3 (one part was in the “knob” and the other was near the threefold vertex). The reported epitopes highly overlapped with our predicted epitopes indicating the predicted results were reliable. These data suggested that three-site distribution pattern may be the basic distribution role of epitopes on the enteroviruses capsids. Our prediction results of EV-A71 and CV-A16 can provide essential information for monitoring the antigenic evolution of enterovirus.

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HDL modification by secretory phospholipase A2 promotes scavenger receptor class B type I interaction and accelerates HDL catabolism

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)31979-9 ◽

2000 ◽

Vol 41 (11) ◽

pp. 1849-1857 ◽

Cited By ~ 11

Author(s):

Frederick C. de Beer ◽

Patrice M. Connell ◽

J. Yu ◽

Maria C. de Beer ◽

Nancy R. Webb ◽

...

Keyword(s):

Phospholipase A2 ◽

Scavenger Receptor ◽

Type I ◽

Secretory Phospholipase A2 ◽

Secretory Phospholipase ◽

Scavenger Receptor Class ◽

Class B

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Molecular epidemiology of coxsackievirus A16 circulating in children in Beijing, China from 2010 to 2019

World Journal of Pediatrics ◽

10.1007/s12519-021-00451-y ◽

2021 ◽

Author(s):

Ya-Fang Hu ◽

Li-Ping Jia ◽

Fang-Yuan Yu ◽

Li-Ying Liu ◽

Qin-Wei Song ◽

...

Keyword(s):

Molecular Epidemiology ◽

Evolutionary Rate ◽

Foot And Mouth Disease ◽

Recent Common Ancestor ◽

Rt Pcr ◽

Coxsackievirus A16 ◽

Most Recent Common Ancestor ◽

Etiological Agents ◽

High Level ◽

And Control

Abstract Background Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot and mouth disease (HFMD). This study aimed to investigate the molecular epidemiology and evolutionary characteristics of CVA16. Methods Throat swabs were collected from children with HFMD and suspected HFMD during 2010–2019. Enteroviruses (EVs) were detected and typed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and RT-PCR. The genotype, evolutionary rate, the most recent common ancestor, population dynamics and selection pressure of CVA16 were analyzed based on viral protein gene (VP1) by bioinformatics software. Results A total of 4709 throat swabs were screened. EVs were detected in 3180 samples and 814 were CVA16 positive. More than 81% of CVA16-positive children were under 5 years old. The prevalence of CVA16 showed obvious periodic fluctuations with a high level during 2010–2012 followed by an apparent decline during 2013–2017. However, the activities of CVA16 increased gradually during 2018–2019. All the Beijing CVA16 strains belonged to sub-genotype B1, and B1b was the dominant strain. One B1c strain was detected in Beijing for the first time in 2016. The estimated mean evolutionary rate of VP1 gene was 4.49 × 10–3 substitution/site/year. Methionine gradually fixed at site-23 of VP1 since 2012. Two sites were detected under episodic positive selection, one of which (site-223) located in neutralizing linear epitope PEP71. Conclusions The dominant strains of CVA16 belonged to clade B1b and evolved in a fast evolutionary rate during 2010–2019 in Beijing. To provide more favorable data for HFMD prevention and control, it is necessary to keep attention on molecular epidemiological and evolutionary characteristics of CVA16.

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