Identification of a Human SCARB2 Region That Is Important for Enterovirus 71 Binding and Infection
JOURNAL OF VIROLOGY
Authors: Yamayoshi, Seiya; Koike, Satoshi
Abstract
We previously identified human scavenger receptor class B, member 2 (SCARB2), as a cellular receptor for enterovirus 71 (EV71). Expression of human SCARB2 (hSCARB2) permitted mouse L929 cells to efficiently bind to virions and to produce both viral proteins and progeny viruses upon EV71 infection. Mouse Scarb2 (mScarb2) exhibited 85.8% amino acid identity and 99.9% similarity to hSCARB2. The expression of mScarb2 in L929 cells conferred partial susceptibility. Very few virions bound to mScarb2-expressing cells. The viral titer in L929 cells expressing mScarb2 was approximately 40- to 100-fold lower than that in L929 cells expressing hSCARB2. Using hSCARB2-mScarb2 chimeric mutants, we attempted to map the region that was important for efficient EV71 infection. L929 cells expressing chimeras that carried amino acids 142 to 204 from the human sequence were susceptible to EV71, while chimeras that carried the mouse sequence in this region were not. Moreover, this region was also critical for binding to virions. The determination of this region in hSCARB2 that is important for EV71 binding and infection greatly contributes to the understanding of virus-receptor interactions. Further studies will clarify the early steps of EV71 infection.
A safe and sensitive enterovirus A71 infection model based on human SCARB2 knock-in mice
VACCINE
Authors: Zhou, Shuya; Liu, Qiang; Wu, Xing; Chen, Pan; Wu, Xi; Guo, Yanan; Liu, Susu; Liang, Zhenglun; Fan, Changfa; Wang, Youchun
Abstract
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 pseudo type 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. (C) 2016 Elsevier Ltd. All rights reserved.