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Findings point to potential treatment for virus causing childhood illnesses

Thu, 01/30/2014 - 7:44am

These images illustrate antibody "footprints" outlined in yellow on the surface of a virus called EV71. Three distinct proteins—out of a total of 180—that make up the viral capsid are outlined in blue, green and red. The neutralizing antibodies E18 (A) and E19 (B), used in this study were found to bind to the viral proteins where the colors are bright. The E18 antibody causes the viral capsid to open, resulting in the loss of the viral genome, suggesting the virus no longer has the ability to replicate in the human host. Image: Dept. of Biological Sciences, Purdue Univ.Researchers have discovered a potential treatment for a viral infection that causes potentially fatal brain swelling and paralysis in children. The findings also point to possible treatments for related viruses including those that cause common cold symptoms.

The virus, called enterovirus 71 (EV71), causes yearly outbreaks of hand, foot and mouth disease in Southeast Asian countries, including China and Malaysia. Some of the infected children develop encephalitis that can be fatal or result in permanent brain damage. There are no anti-EV71therapeutic agents available.

The researchers prepared antibodies by immunizing mice with immature EV71 particles. Antibodies generated by this immunization induced a change in the mature EV71 virus, rendering it non-infectious by causing the virus particles to lose their genome.

The findings reveal a potential treatment mechanism, demonstrating that the antibody, called E18, has potential as an anti-EV71 therapy, said Michael G. Rossmann, Purdue's hanley distinguished prof. of biological sciences.

Findings are being reported in Proceedings of the National Academy of Sciences.

EV71 belongs to a family of viruses called picornaviruses, pathogens that cause diseases including common-cold-like illnesses and poliomyelitis in people and chronic infections in livestock.

"The antibody-mediated virus neutralization by the induction of genome release has not been previously demonstrated," Rossmann said. "These results indicate that antibodies with genome-release activity could also be produced for other picornaviruses by immunization with immature particles. The approach could be used to prepare antibodies with similar properties against related viruses that include significant human pathogens."

Researchers observed and documented the loss of genome using two laboratory techniques: cryo-electron microscopy and a fluorescent SYBR Green dye assay.

Hand, foot and mouth disease, an infection most common among young children, sometimes arises in a daycare setting. Of the 427,278 cases of the disease recorded in China between January and May 2010, 5,454 cases were classified as severe, with 260 deaths, according to the World Health Organization.

Source: Purdue Univ.

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