Enterovirus D-68 Infection of Primary Rat Cortical Neurons: Entry, Replication, and Functional Consequences

Katrien C. K. Poelaerta, Regina G. D. M. van Kleefb, Mengying Liua, Arno van Vlieta, Heyrhyoung Lyooa, Lora-Sophie Gerberb, Yoshiki Narimatsuc, Christian Büllc, Henrik Clausenc, Erik de Vriesa, Remco H. S. Westerinkb, Frank J. M. van Kuppevelda

American Society for Microbiology, 6 March 2023

Researchers use the Maestro MEA platform to assess the effects of AFM-associated enterovirus D-68 infection on neuronal networks.  

Enterovirus D-68 (EV-D68) is typically associated with mild to severe respiratory illness but since 2014 has also been linked to acute flaccid myelitis (AFM)—a serious neurologic condition causing muscle weakness and sometimes permanent paralysis in children. Scientists are unsure if AFM cases over the past decade reflect increased pathogenicity of the virus or simply increased awareness and detection. In this study, researchers generate an in vitro infection model of primary rat cortical neurons to investigate neurotropism, receptor usage, replication, cell health, and functional consequences on neuronal networks associated with historical and contemporary EV-D68 strains. 

Using Axion’s noninvasive Maestro multielectrode array (MEA) platform, the researchers demonstrated that enterovirus infection results in decreased spontaneous neural activity of neuronal networks in vitro. Importantly, the authors did not observe differences in neural activity when comparing the effects of infection with historical versus circulating strains, suggesting that “the association of EV-D68 with neurological disease is unlikely due to specific changes in virus strains to infect neuronal cells, but more likely due to increased ability of the virus to reach the CNS, or due to increased circulation of EV-D68 in the population.” Overall, the results provide novel insights into EV-D68 and its related neurological effects.