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The Making of Medicine

Why Cold Sores Flare When You Get Sick or Sunburned

Cold sores often flare up at the worst possible time, and our researchers have shed light on why.

Once you’re infected with herpes simplex virus (HSV), the virus never really goes away. Instead, it lurks inside your neurons, waiting to flare up again. This is called reactivation.

Doctors have known that reactivation is associated with stress, illness and sunburn, but they haven't really understood why.

Our Anna R. Cliffe, PhD, of the Department of Microbiology, Immunology and Cancer Biology, and her team found answers. When neurons harboring the virus are exposed to stimuli that induce “neuronal hyperexcitation,” the researchers determined, the virus senses this particular change.

Using a mouse model developed in their lab, the researchers determined that the virus highjacks an important immune response within the body. In response to prolonged periods of inflammation or stress, the immune system releases a particular cytokine, Interleukin 1 beta.

Interleukin 1 beta then increases the excitability in the affected neurons, setting the stage for HSV to flare up.

“It is really remarkable that the virus has hijacked this pathway that is part of our body’s immune response,” Cliffe said. “It highlights how some viruses have evolved to take advantage of what should be part of our infection-fighting machinery.”

The new insights help doctors better understand what is happening in neurons and the immune system, and that could lead to ways to prevent unwanted outbreaks, the researchers hope. That would be good news for a lot of people, considering half of Americans harbor the virus. (The numbers are even higher in other parts of the world.)

“A better understanding of what causes HSV to reactivate in response to a stimulus is needed to develop novel therapeutics,” Cliffe said. “Ultimately, what we hope to do is target the latent virus itself and make it unresponsive to stimuli such as Interleukin 1 beta.”

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