We go back a long way with herpesviruses. Our evolutionary line has been living with these genomic parasites for more than 100 million years, and today herpesviruses infect nearly all humans, as well as all other mammals, birds and reptiles that scientists have checked. We aren't born with these viruses, but most of us acquire multiple infections of various types of herpesviruses during childhood.
Unlike our relationship with many other, more notorious viruses, we've learned to peacefully coexist with herpesviruses for the most part. They set up shop in our cells, they use our molecular machinery to replicate themselves, and they take advantage of the influx of energy we provide from our diet. Sometimes the relationship goes sour, with the unfortunate results ranging from chickenpox to mononucleosis, genital herpes, and Burkitt's lymphoma, but by and large, most humans, and mammals in general, are never seriously harmed by these house guests. But do we get anything out of this relationship? Remarkably, recent research suggests that this 100 million-year coexistence may have been good for us too, helping our immune system to ward off even more serious pathogens.
When we first become infected by a herpesvirus, we often feel the effects as we come down with shingles or mono. But after our immune system fights off this acute infection, the virus hunkers down and enters a subdued, latent phase. During latency, the virus doesn't do much more than get its genome replicated by our cells, and the preferred herpes hangout during this time is inside a type of immune cell called a macrophage.
Macrophages make up our microscopic version of the US Marine Corps: they are merciless killing machines that go after the bacterial pathogens that threaten us. But macrophages aren't primed to fight all the time. They need to be stimulated by immune system hormones, such as one called interferon-gamma (IFN-gamma). When we become infected with a pathogen, we produce these macrophage-stimulating hormones, which leads the macrophages to gear up and take on the infection.
So what do latent herpesviruses have to do with any of this? Latent viruses are not entirely peaceful; they do have a nasty habit of reactivation, especially under times of stress, and then the human host is faced with an acute infection that can produce symptoms. This acute infection has to be suppressed all over again, and obviously our immune systems would prefer to just keep the viruses latent forever.
To do this, it appears that our bodies produce the macrophage-stimulating IFN-gamma in response to latent infections. Much like the US Department of Homeland Security Threat Level, which never seems to dip below the yellow "Elevated", our levels of IFN-gamma remain elevated in the presence latent herpesvirus infections, which keeps the macrophages primed to suppress the virus when it gets uppity.
Dr. Herbert Virgin, at the Washington University School of Medicine, has discovered that this persistently elevated level of IFN-gamma is actually helpful in warding off some serious diseases. He took two sets of mice, one set which was latently infected with a herpesvirus, and another set that had never been exposed to these viruses, and he injected them with some nasty pathogens: listeria and Yersinia pestis, the bacteria that causes plague. The mice without the latent herpesvirus generally died off quickly, but amazingly, the mice which did have herpesviruses hanging out in their macrophages frequently survived these nasty infections. It appears that latent viruses cause us to produce IFN-gamma, which in turn helps us (or at least mice) survive bacterial infections.
Dr. Virgin has taken this even further, just to show how key IFN-gamma is in this whole scenario. As we just saw, mice which have latent viral infections can fight off the plague. But the herpesvirus fails to have any protective effect in mutant mice that can't produce IFN-gamma, demonstrating that IFN-gamma is the key component. It all boils down to this:
1. Mice with latent viral infections produce more IFN-gamma than mice that haven't been exposed to the virus.
2. Mice with latent viral infections can fight off nasty bacteria better than mice without the virus.
3. But even mice with the virus aren't helped if they don't make IFN-gamma, showing conclusively that IFN-gamma is the key player.
While these experiments have only been done in lab mice, the immune system components are vert similar to what exists in humans, so it's likely that this protective effect exists in us. In fact, it is likely to be found in most mammals, because, as Dr. Virgin argues, this effect is a response that evolved a long time ago - we've been living with herpesviruses since before we were mammals. So when your chickenpox-infected kid is keeping you up with complaints in the middle of the night, or you're wiped out with mono, remind yourself that our relationship with herpesviruses, while it has its ups and downs, is worth the long-term committment.
For more, check out Dr. Virgin's paper in Nature.