A safe and sensitive enterovirus A71 infection model based on human SCARB2 knock-in mice.
Enterovirus A71 infection has become a severe threat for global public health. Vaccines for controlling and preventing Enterovirus A71 epidemics are highly demanded, however, vaccine evaluation has been hindered by the lack of suitable Enterovirus A71 infection animal models. Here we established an hSCARB2 knockin mouse model for real-time monitoring of enterovirus A71 infection in vivo. This model was sensitive to the infection of both replication-competent virus rEV71(FY)-EGFP and single round pseudotype virus pEV71(FY)-Luc. The intensity of bioluminescence correlated well with viral loads in infected tissues (R=0.86, P<0.01). Pathological changes recapitulated human infectious and clinical features of enterovirus A71, including both general characteristics of "hand foot and mouth" and the severe symptoms in the CNS. A formalin-inactivated enterovirus A71 vaccine can elicit antibodies in R26-hSCARB2 mice, which play effective roles in protecting knockin mice against enterovirus A71 infection as indicated by bioluminescence. Therefore, this work provides a safe, sensitive and visualizing model for exploring mechanisms of enterovirus A71 infection and examining human enterovirus A71 vaccines and antiviral therapies.
Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, 100050, China.
Shuya
S
Zhou
Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, 100050, China.
Qiang
Q
Liu
Division of Hepatitis Vaccine, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, 100050, China.
Xing
X
Wu
Division of Hepatitis Vaccine, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, 100050, China.
Pan
P
Chen
Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, 100050, China.
Xi
X
Wu
Biocytogen Co., Ltd., Beijing, 101111, China.
Yanan
Y
Guo
Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, 100050, China.
Susu
S
Liu
Division of Hepatitis Vaccine, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, 100050, China.
Zhenglun
Z
Liang
Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, 100050, China.
Changfa
C
Fan
Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, 100050, China. Electronic address: wangyc@nifdc.org.cn.
Youchun
Y
Wang
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D029821:Enterovirus A, Human; D005260:Female; D055879:Gene Knock-In Techniques; D006232:Hand, Foot and Mouth Disease / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D008163:Luminescent Measurements; D051907:Lysosomal Membrane Proteins / Q000235:genetics; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D051116:Receptors, Scavenger / Q000235:genetics; D015164:Vaccines, Inactivated / Q000276:immunology; D019562:Viral Load; D014765:Viral Vaccines / Q000276:immunology
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D051907:Lysosomal Membrane Proteins; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; D015164:Vaccines, Inactivated; D014765:Viral Vaccines
Bioluminescent imaging; Enterovirus A71 mouse model; Pseudotype virus; Vaccine effect evaluation; hSCARB2 knockin