Neuron Preservers

Unlike epithelial cells, neurons respond to herpes infection through autophagy, rather than by releasing inflammatory factors.

Jan 1, 2013
Kerry Grens


SKIRTING DEATH: Most cells infected with herpes virus die to prevent viral spread. Infected neurons, pictured here, undergo autophagy instead.COURTESY OF BRIAN YORDY

The paper
B. Yordy et al., “A neuron-specific role for autophagy in antiviral defense against herpes simplex virus,” Cell Host & Microbe, 12:334-45, 2012.

The problem
Activation of the immune system by interferons is important in battling viral infections, but it can also result in cell death—a path that spells trouble for infected nonrenewable cell types, such as neurons. It’s been shown that neurons can instead rely on autophagy to gobble up viral particles and stop infections, but it was unclear whether this response was critical to protecting neurons and whether it was a general mechanism used by other cell types.
The finding
Akiko Iwasaki at Yale University School of Medicine and her colleagues conducted a comparison of two cell types by infecting mice with herpes simplex type-1, which affects both epithelial and peripheral nerve cells. The group engineered mice with either an epithelial-cell or neuronal knockout of a gene called Atg5, which is required for autophagy. In engineered epithelial cells, there was no effect on viral replication. In contrast, engineered nerve cells exhibited a roughly 10-fold increase in viral replication compared to nerve cells with a functional autophagy pathway.

The implication
“This demonstrates that autophagy is important in controlling the viral infection in neurons, but not in epithelial cells,” says Beth Levine, a professor at the University of Texas Southwestern, who was not part of the study. Taking a route other than the typical interferon response—which results in apoptosis of the infected cell—gives neurons an opportunity to skirt cell death while taking down a virus.

The application
“We are far from directly applying this to the clinic, but our study shows if you can induce autophagy in neurons, we might be able to prevent infection from herpes virus,” says Iwasaki.