The Upside of Herpes — When One Infection Protects Against Another

In mice at least, Herpes provides resistance against bacteria, including the bubonic plague.

Not Exactly Rocket Science
By Ed Yong
Feb 21, 2009 5:00 PMMay 2, 2023 5:54 PM
Cold sore
(Credit: Africa Studio/Shutterstock)


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When people say that every cloud has a silver lining, they probably aren’t thinking about herpes at the time. Herpes may be unpleasant, but the viruses that cause it and related diseases could have a bright side. In mice at least, they provide resistance against bacteria, including the bubonic plague.

Herpes is one of a number of itchy, blistering diseases, caused by the group of viruses aptly-named herpesviruses. Eight members infect humans and cause a range of illnesses including glandular fever, chickenpox, shingles and, of course, herpes itself.

Almost everyone gets infected by one of these eight during their childhood. But herpesviruses are for life, not just for Christmas. After your body fights off the initial infection, the virus retreats into a dormant phase known as ‘latency’. It remains hidden and causes no symptoms, but has the potential to reactivate at a later date. In this way, herpesviruses can seem like life-long parasites, ensuring their own survival at the cost of their host’s future health. In extreme cases, latent viruses can lead to chronic inflammation, which in turn can cause autoimmune diseases, or some types of cancer.

But there is a bright side too. Erik Barton and colleagues from Washington University Medical School found that once infected mice entered the latent stage, they were surprisingly resistant to certain types of bacteria. Unlike their vulnerable uninfected peers, they even managed to ward off the deadly plague bug, Yersinia pestis.

At least in mice, latent herpesviruses turn out to be paying tenants rather than free-loading squatters — bacterial resistance is their rent. The latent stage is crucial to the resistance effect, and Barton found that a mutant herpesvirus that infects but doesn’t set up shop provides no benefits to its host.

The viruses work their magic by putting the immune system on high alert. The effect is similar to a raising of the terror alert creating a heightened level of security where the body is prepared to fight off any further threats.The viruses trigger the release of high levels of immune system chemicals called cytokines. These molecules — including interferon-gamma (IFN-g) and tumor necrosis factor alpha (TNF-a) — help to co-ordinate the defense against infections.

These chemicals activate macrophages — a type of white blood cell. These cellular assassins engulf invading bacteria, and sentence them to death by digestion. And in mice latently infected by herpesviruses, they are activated in bulk. This sequence is similar to the way the immune system normally protects us against multiple bacterial invaders. But in Barton’s experiments, the protection was set off by viruses instead, and lasted for much longer than normal.

All well and good for the mice, but do these viruses benefit us too? Barton thinks so. In his study, two very different strains — murine gammaherpesvirus 68 (gHV68) and murine cytomegalovirus (MCMV) — had the same effect. He believes that providing bacterial resistance is a general property of all herpesviruses.

There is certainly growing evidence to support his claims. If many people, the latent viruses reactivate regularly, but not strongly enough to cause major symptoms. In these cases, doctors have seen higher levels of cytokines and long-term activation of the immune system, just like Barton saw in his mice.

Barton even suggests that herpesvirus infection may play a role in protecting against allergies. According to the ‘hygeine hypothesis‘, infections during childhood prime the immune system against future threats. By depriving children of these experiences, overly clean homes can lead to naïve immune systems that react disproportionately to harmless things like pollen. Allergies are the result.

It isn’t clear what role herpesviruses play in priming the immune system. But at least one study found that people who are infected with the Epstein-Barr herpesvirus (EBV) are less likely to show sensitive antibody reactions to allergens in their environment. Clearly, the subject is a rich vein for further research.

Almost everyone has had an encounter with a herpesvirus of some kind. They cause a wide range of diseases, but could they be protecting us from many more?

Reference: Barton, White, Cathelyn, Brett-McClellan, Engle, Diamond, Miller & Virgin IV. 2007. Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 447: 326-330.

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