Thursday, 18 October 2018 17:14

Enterovirus D68 Infects Human Neuronal Cells and Cause Paralysis in Mice

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Published in mBiosphere

CDC chart of acute flaccid paralysis casesNumber of acute flaccid myelitis cases confirmed by the CDC as of October 16, 2018. Source.

This year has seen an unusual number of cases of acute flaccid myelitis (AFM), a symptom in which patients—normally children—experience the inability to move lower extremities. Cases have been increasing since 2014, with seasonal peaks in late summer or early fall months (see graph, right). In some cases patients recover quickly, but in others, patients develop long-term paralysis and require continued care. One of the leading candidates for the cause of these AFM outbreaks is enterovirus D68 (EV-D68). New supporting evidence of the role of EV-D68 comes from an mBio study demonstrating that EV-D68 can replicate in human neuronal cells.

 

mBio: Contemporary Circulating Enterovirus D68 Strains Have Acquired the Capacity for Viral Entry and Replication in Human Neuronal Cells

 

The scientific team, led by first author David Brown and senior author Richard Scheuermann, demonstrated that some EV-D68 isolates are better able to infect a human neuroblastoma cell line than others. Three different EV D-68 isolates were tested, including 2 currently circulating strains of different lineages (called clade A and clade B) and a historical isolate similar to the original EV-D68 isolate identified in 1962. Clade B EV-D68 strains were isolated during the 2014 EV-D68 outbreak and are thought to be associated with AFM; of the 3 tested viruses, only the clade B strain, called US/MO/47, was able to replicate in and cause damage to the neuronal cell line.

 

Effect of clade B EV-D68 infection on mouse motor activityEffect of clade B enterovirus D68 infection on mouse motor function. Source.

The EV-D68 strain that caused damage to human neuronal cells also caused neuropathogenic disease in mice (see graph, right). All mice infected with US/MO/47 developed paralysis and had high viral titers in both their muscle and spinal cord tissues. No mice infected with other EV-D68 strains developed signs of paralysis or had detectable virus in their spinal cords. While mouse models aren’t always a perfect representation of disease in humans, the similar symptoms add another layer of support for a role of EV-D68 in AFM.

 

The mBio work also points to an important step in viral replication that may be important to block disease. The neurotropic EV-D68 strain bound to human neuronal cells better than the other strains, but when the viral genome was transformed into the neuronal cells, cells infected with any of the EV-D68 strains expressed viral proteins and produced progeny virions. This suggests that viral binding or internalization is critical for neuronal damage to occur.

 

This data doesn’t directly tie EV-D68 to the current outbreak of AFM, but adds to a growing body of literature that supports EV-D68 may cause AFM. Despite testing for a variety of pathogens, the Centers for Disease Control and Prevention have been unable to consistently detect EV-D68 or other potential pathogenic causes of this outbreak among patients. EV-D68 often infects people without causing disease, but can cause upper respiratory infections in people of all ages; the best way to avoid infection is to wash your hands regularly and avoid touching your eyes, nose or mouth.

 

Cover image credit

Last modified on Thursday, 18 October 2018 17:40
Julie Wolf

Julie Wolf is the ASM Science Communications Specialist. She contributes to the ASM social media and blog network and hosts the Meet the Microbiologist podcast. She also runs workshops at ASM conferences to help scientists improve their own communication skills. Follow Julie on Twitter for more ASM and microbiology highlights at @JulieMarieWolf.

Julie earned her Ph.D. from the University of Minnesota, focusing on medical mycology and infectious disease. Outside of her work at ASM, she maintains a strong commitment to scientific education and teaches molecular biology at the community biolab, Genspace. She lives in beautiful New York City.

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