Abstract
BackgroundEnterovirus A71 (EV-A71) is a neurotropic virus which may cause severe neural complications, especially in infants and children. The clinical manifestations include hand-foot-and-mouth disease, herpangina, brainstem encephalitis, pulmonary edema, and other severe neurological diseases. Although there are some vaccines approved, the post-marketing surveillance is still unavailable. In addition, there is no antiviral drugs against EV-A71 available.MethodsIn this study, we identified a novel antibody that could inhibit viral growth through a human single chain variable fragment (scFv) library expressed in mammalian cells and panned by infection with lethal dose of EV-A71.ResultsWe identified that the host protein α-enolase (ENO1) is the target of this scFv, and anti-ENO1 antibody was found to be more in mild cases than severe EV-A71 cases. Furthermore, we examined the antiviral activity in a mouse model. We found that the treatment of the identified 07-human IgG1 antibody increased the survival rate after virus challenge, and significantly decreased the viral RNA and the level of neural pathology in brain tissue.ConclusionsCollectively, through a promising intracellular scFv library expression and screening system, we found a potential scFv/antibody which targets host protein ENO1 and can interfere with the infection of EV-A71. The results indicate that the usage and application of this antibody may offer a potential treatment against EV-A71 infection.
Highlights
Enterovirus A71 (EV-A71) is a neurotropic virus which may cause severe neural complications, espe‐ cially in infants and children
It may not be easy to identify whether these Single chain variable fragment (scFv) could protect against EV-A71 infection in cells
After the removal of supernatants, the scFv which exist in intracellular compartment can help us to screen for antibody against EV-A71 after infection
Summary
Enterovirus A71 (EV-A71) is a neurotropic virus which may cause severe neural complications, espe‐ cially in infants and children. The clinical manifestations include hand-foot-and-mouth disease, herpangina, brainstem encephalitis, pulmonary edema, and other severe neurological diseases. Enterovirus A71 (EV-A71), a subtype virus of Enterovirus A species belonging to the Enterovirus genus in the Picornaviridae family, is a major causative agent of viral hand-foot-and-mouth disease (HFMD) and herpangina in infants and children. The variable region of heavy chain (VH) and light chain (VL) consist of interlaced complementarity determining regions (CDRs) and framework region (Fw). This variable fragment (Fv) is the major and smallest binding domain to specific antigen. Some limitations of intact antibody facilitate the application of single chain variable fragment (scFv) by joining the V H
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