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Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD), which can lead to severe neurological complications such as brainstem encephalitis and pulmonary edema (Plevka et al., Science 2012). The viral capsid is an icosahedral structure composed of 60 protomers, each containing the structural proteins VP1, VP2, VP3, and VP4. The VP2 puff (EF loop) and VP3 knob (BC loop) are prominent surface-exposed regions that serve as critical antigenic determinants for the virus (Wang et al., Nat Struct Mol Biol 2012). These regions are essential for viral fitness as they are involved in the interaction with host cell receptors, including SCARB2 and PSGL-1, and facilitate the structural transitions necessary for viral uncoating (Yamayoshi et al., Nature 2009). Because of their high accessibility on the virion surface, the VP2 puff and VP3 knob are primary targets for neutralizing antibodies elicited by both natural infection and inactivated vaccines. Therapeutic development focuses on these regions to design monoclonal antibodies that can prevent viral entry or to monitor the efficacy of immunization programs against emerging viral variants (Shingler et al., J Virol 2013).
Induction of neutralizing antibodies that bind to surface-exposed loops to block viral attachment to host receptors or inhibit the conformational changes required for viral uncoating.
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