Key Protein That Makes EV71 Viral Infection Virulent

Prohibitin, a human protein may play a significant role in infection of the nervous system by EV71. The virus, EV71 can cause hand, foot, and mouth disease.

Hand, foot, and mouth disease are usually mild, with symptoms such as skin rash and fever. However, especially if caused by EV71, it sometimes leads to neurological complications in young children.

Sore Throat Symptom Evaluation

Sore throat is a common symptom that usually affects people during a weather change. It is often caused by a viral infection.

‘Prohibitin found on the surface of motor neuron cells was involved in entry of EV71.’

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EV71 is closely related to poliovirus and has recently received increased attention due to its life-threatening effects. Yet, the molecular mechanisms behind EV71 nervous system infection remain unclear.

To better understand these mechanisms, Too and colleagues infected human motor neuron cells with EV71 and compiled a list of human proteins that showed changes in activity during infection. Additional experiments, including gene knockdown, surfaced prohibitin as a likely infection aide; prohibitin is a multi-functional protein found in human cells and in many other organisms.

Mumps

Mumps is a contagious viral infection that typically causes a painful swelling of one or more of the salivary gland. Mumps most commonly occurs in children aged 2-12 years who have not been vaccinated against the disease. However, it can occur at any age. It was a common childhood disease before the development of the mumps vaccine (MMR vaccine).

The research team then used a variety of molecular biology techniques to investigate prohibitin's precise role in EV71 nervous system infection. They demonstrated that prohibitin found on the surface of motor neuron cells was involved in entry of EV71 into those cells. Within the cells, prohibitin associated with mitochondria was required for the virus to replicate itself.

Next, the team explored the effects of an anti-cancer drug known as Rocaglamide (Roc-A), which is known to inhibit the activity of prohibitin. They found that treating EV71-infected neuronal cells with Roc-A resulted in significantly lower cellular levels of the virus than seen in untreated cells. Furthermore, EV71-infected mice given Roc-A lived longer than untreated mice and had lower levels of the virus in their spinal cord and brain.

These findings suggest that prohibitin may play a pivotal role in EV1 infection of the nervous system in humans. Repurposing Roc-A or developing new drugs to target prohibitin could potentially help prevent or limit the neurological complications of EV71 infection. Further research is needed to refine understanding of prohibitin's molecular role and corresponding treatment possibilities.

"This study identifies PHB as the first host factor that is specifically involved in EV71 infection of the CNS," the authors further explain. "PHB is a druggable target (targeted by Rocaglamide) and as such, it is hoped that our work paves the way towards an effective treatment able to prevent the neurological complications associated with EV71 infections."

Source: Eurekalert