Secrets of shingles revealed by new animal model

Researchers tin can now see how chickenpox virus behaves in human nerve cells

By Krista Conger

Ann Arviin

Nigh of us have a time bomb nestled inside our nervus cells, waiting for our immune system to stammer in the face up of historic period or illness.

If you lot've had craven pox, you're at risk for shingles – a painful nerve disorder that can make the slightest breeze or bear upon excruciating. People over the age of eighty have a one in five gamble of being affected, and every passing twelvemonth increases the risk.

At that place may exist promise on the horizon, though. Medical center researchers have developed the first creature model to study how the culprit, the varicella-zoster virus, negotiates an uneasy truce with our nerve cells that can last for decades after the spotty childhood rash fades.

Further research may let the scientists to modify an existing vaccine to go far less probable to spark a shingles flare-upwards, or fifty-fifty to improve the shingle-free odds of those of us already playing unwilling hosts to the virus.

Until at present, research has been hampered by the fact that the virus is particularly picky in its choice of hosts: holding out for real human nerve cells rather than settling for those of any garden-variety enquiry animal. Those in a culture dish weren't upwardly to the task of mimicking an ongoing infection, either.

So Stanford scientists, led past pathology professor Irving Weissman, Doc, devised a manner to incorporate human nerve cells into the brains of mice.

"We can now see the beliefs of the virus in human neurons for the first fourth dimension," said Ann Arvin, MD, main of pediatric communicable diseases at Lucile Packard Children'southward Hospital and professor of pediatrics and of microbiology and immunology.

Arvin is the senior author of the enquiry, which was published online in the Proceedings of the National Academy of Sciences in early July.

The double whammy dished out past varicella-zoster virus makes it particularly of import to sympathize the requite-and-take between virus and host.

Although a modified, weakened version of the virus has been developed to protect healthy children against total-blown craven pox, the vaccination can sometimes cause later episodes of shingles in children whose immune systems are compromised by cancer or organ transplantation. The risk of reactivation, however, is lower for vaccinated children than for those who were naturally infected with the wild-type virus.

"We can use this model to empathize which viral genes are important for infecting neurons," said Arvin. "If we can get rid of those genes in the virus used for the vaccine, we might be able to prevent reactivation."

The researchers found that, every bit expected, the weakened virus used for the vaccine was capable of infecting the human neurons in the brains of the mice.

One time established, both the wild type and the vaccine version of the virus can too spread between neurons.

"Nosotros found that if the virus got into one jail cell, information technology seems to be able to infect nearby cells, presumably increasing its chances of reactivation," said Arvin, who holds the Lucile Salter Packard Professorship in Pediatrics.

"It too behaves very differently in neurons than it does in pare cells: in pare information technology destroys the cells, whereas in neurons it seems to gear up up a kind of infection that allows it to persist for the lifetime of the private," she added.

The fact that the mice used in the study accept non-functioning allowed systems is also telling. Information technology was previously thought that a robust immune response was the key to preventing an attack of shingles immediately after infection.

"Clearly all of this is taking place without any of the usual types of active allowed responses," said Arvin. "These findings propose that the neuron itself has a manner of all-around the virus – a kind of temporarily mutually beneficial human relationship that allows the neuron to escape destruction even while the virus persists."