Doctors see them as harmless hitchhikers at best and dangerous pathogens at worst. But a new study of mice shows that herpesviruses, which most of us carry for life, may have a surprising benefit: They offer protection from bacterial pathogens, including the one that causes plague. The effect is a rare example of a beneficial relationship between a virus and its host, the researchers say.
Eight human herpesviruses are known, and most people are infected with several of them at an early age. They can cause serious disease: The cytomegalovirus (CMV), for instance, can blind people with compromised immune systems, and the Epstein-Barr virus (EBV) can cause tumors. But in the vast majority of cases, herpesviruses become latent: They just hang out in the body, never leaving but never causing trouble.
A key player in maintaining this equilibrium is a host molecule called interferon-γ (IFN-γ). But that's not all it does. IFN-γ also helps fight bacterial infection by activating macrophages, a type of white blood cell that gobbles up microbes. So viral immunologist Herbert Virgin of Washington University School of Medicine in St. Louis, Missouri, reasoned that latently infected mice might be more resistant to bacterial infection, because those mice have higher blood levels of IFN-γ.
The hunch proved right, at least for two of the three subfamilies of herpesviruses. Mice latently infected with a so-called betaherpesvirus or a gammaherpesvirus were highly resistant to infection with Listeria monocytogenes, a food-borne microbe, and with Yersinia pestis, the plague bacterium, Virgin and his colleagues found. (Control animals developed a severe infection after exposure to either bug.) Latent infection with the third subfamily--alphaherpesvirus--did not offer such protection, the team reports tomorrow in Nature.
Determining whether the same is true in humans will be a challenge, says Virgin, if only because it will be difficult to find enough people who have never been infected with any beta- or gammaherpesvirus. But if the viruses protect humans too, researchers would need to look at them in a new way, says Virgin. After coevolving with their hosts for 100 million years, "you could argue that they are part of our normal flora," he says, like the microbes living in our guts. And vaccines now in development against CMV and EBV may have to be studied more carefully, he notes, because they could increase the long-term risk of bacterial infections.
There are a few other examples of one pathogen warding off another, says Jacob Koella, who studies host and parasite evolution at Imperial College London. For instance, schistosomiasis, a parasitic disease, appears to protect its host against malaria. But this is the first example of a do-good virus, he says. Still, many more of these evolutionary tradeoffs may exist, Koella predicts: "It's something that not enough people are thinking about."