Cross-Reactive Antibody Responses against Nonpoliovirus Enteroviruses

Enteroviruses are among the most common human viral pathogens. Infection with members of a subgroup of viruses within this genus, the nonpoliovirus enteroviruses (NPEVs), can result in a broad spectrum of serious illnesses, including acute flaccid myelitis (AFM), a polio-like childhood paralysis; neonatal sepsis; aseptic meningitis; myocarditis; and hand-foot-mouth disease. Despite the diverse primary sites of virus infection, including the respiratory and alimentary tracts, and an array of diseases associated with these infections, there is significant genetic and antigenic similarity among NPEVs. This conservation results in the induction of cross-reactive antibodies that are either able to bind and neutralize or bind but not neutralize multiple NPEVs. Using plaque reduction and enzyme-linked immunosorbent assay (ELISA)-based binding assays, we define the antigenic relationship among poliovirus and NPEVs, including multiple isolates of EV-D68, EV-A71, EV-D70, EV-94, EV-111, Coxsackievirus A24v, and rhinovirus. The results reveal extensive cross-reactivity among EVs that cannot be predicted from phylogenetic analysis. Determining the immunologic relationship among EVs is critical to understanding the humoral response elicited during homologous and heterologous virus infections.