Hiding in Plain Sight
When the United States began vaccinating against the measles virus in the 1960s, children fortunately stopped getting measles. But that wasn’t the only thing; suddenly, American children had plummeting risks of dying from all sorts of other infectious diseases, too. The same thing happened in European countries joining the effort. But how can a vaccine protect against infections that it’s not even targeting?
Like all other microbes that infect us, the measles virus is not a big fan of our immune system. Cells of the immune system are constantly on the lookout for invaders and will spring into action if an uninvited guest is discovered. Viruses like the measles virus fight back by hiding, by trying to trick the immune system and sometimes also by counterattack. This war between our immune system and various microbes is ongoing throughout our lives. It’s happening inside you at this very moment.
Pathogens have evolved various weapons to target the immune system, but the measles virus has found a particularly effective one. It can cause something you can think of as immune memory loss. Usually, certain cells of the immune system retain a memory of previous adversaries. This is clever, because it decreases the time it takes for the immune system to react if it encounters the same enemy again. Then, there will already be a tried-and-tested battleplan ready for deployment to rob the infection of the chance to take hold. This immune ‘memory’ is the reason vaccines can protect against developing a disease, and also the reason you only get diseases such as chickenpox once in a lifetime.
When the measles virus causes ‘memory loss’ in our immune system, though, all this valuable information is lost. This benefits the measles virus itself, but it’s also a boon for all sorts of other bacteria and viruses. Suddenly, these pathogens have a much easier time infecting us. Therefore, infection with the measles virus predisposes you to all sorts of other infections, too. In fact, it is estimated that the measles virus used to contribute to half of childhood deaths from other infections.
Such one-two punches are quite common in the world of infections. A straight right from an initial infection and then a left hook from a second one that exploits the chaos to its own benefit. On the one hand, this principle illustrates why vaccines were (and still are) the uncrowned king of medical science. But it is also bad news, because there are still plenty of dangerous microbes that we don’t have vaccines against yet.
A particularly good example is HIV, the virus that causes AIDS. HIV attacks certain cells of the immune system called T-cells. You can think of T-cells as the generals of the immune system, because they are responsible for orchestrating your immune responses. When HIV attacks T-cells, they eventually succumb to the virus. This means the immune system becomes weaker and weaker, and eventually it cannot keep up with all sorts of other microbes. As a result, HIV-infected people become vulnerable to otherwise harmless infections. Microbes, which normally live in or on us in peaceful coexistence, sense an opportunity and begin to grow out of control. The relatively harmless fungus Candida albicans – which lives on over half of us – can turn into a serious infection. Herpes virus 8 can go from being relatively harmless to causing a form of cancer called Kaposi’s sarcoma. Even the flu can become deadly.
The infectious burden of HIV is taxing on the body, and even though we now have anti-HIV drugs that help patients live much longer than previously, they still die earlier than non-infected people. They also have an increased risk of everything from cancer to cardiovascular diseases. And in fact, it turns out that HIV infection in itself increases the rate of biological ageing. Patients with HIV are five to seven years older biologically than their actual age as measured by the epigenetic clock.
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Fortunately, we’re still making progress in the fight against HIV, and it is less of a health threat than it used to be. If you take normal precautions, getting infected is highly unlikely. However, there are other much more common infections that can similarly accelerate ageing. In fact, it looks like being infected in and of itself makes us grow old faster. The more and the worse infections you have, the quicker you age. This is probably one of the reasons why people today look so much younger than similarly aged people in the past. A hundred years ago, middle-aged people had lived a life ravished by infections from childhood. That means they looked older – and, frankly, more worn out – than middle-aged people today who have lived a life protected by vaccines.
While we’ve used vaccines to eradicate many of the viruses that used to kill and maim us, there are still nasty ones around today. One example is a virus called cytomegalovirus (CMV). You’ve probably never heard of it before, but it’s actually a very common viral infection. In developing countries, virtually everyone is infected by the time they reach adulthood. In the developed world, infection rates are lower, but the majority of people are still infected at some point in their life.
CMV is a member of the herpes virus family, along with the viruses that cause cold sores. You won’t get cold sores from CMV, but like other herpes viruses, it’s chronic. Once infected, you can never get rid of it again.
CMV is transmitted person-to-person through body fluids and can infect many different cell types in our bodies. After forcing access to a cell, the virus integrates into the cell’s DNA and hijacks the cell for its own purposes. Then it enters a lifecycle that alternates between activity and dormancy. When active, CMV forces infected cells to produce more CMV particles, which can be used to spread the infection to new cells or to new individuals. Our immune system notices when CMV is causing trouble and will try to fight back. However, at any point CMV can retreat back into dormancy, which helps it escape. Then it will hide and wait for its next opportunity to awaken. The chronic nature of a CMV infection drives the immune system absolutely nuts. In infected individuals, up to ten per cent of key immune cells can be occupied trying to contain the virus. That obviously depletes the resources of the immune system and distracts it from other enemies. In this way, CMV increases the likelihood of many other infections.
You’re unlikely to notice any of this, as CMV infections are mostly asymptomatic (except in babies, where they are the leading cause of hearing loss). However, using epigenetic clocks, scientists have found that a CMV infection accelerates the ageing process. It also seems to increase blood pressure long-term and might even promote the development of plaque in arteries. In addition, CMV prevents infected cells from carrying out cellular suicide, increasing their risk of becoming harmful zombie cells.
All of this makes CMV an obvious candidate for eradication by vaccination. However, just as it dodges our actual immune systems, it has also managed to dodge our ‘extended’ immune systems – medical science and the pharmaceutical industry. CMV is annoyingly hard to target, and as it has health consequences that are hidden at first glance, it wasn’t taken seriously enough in the past. Now, though, vaccine efforts have picked up.
Another example of a pathogen that can accelerate the ageing process and lead to disease is CMV’s cousin from the herpes virus family, Epstein-Barr virus (EBV). EBV is also chronic, and it is the virus that causes mononucleosis. It infects pretty much everyone before they reach adulthood. Those who don’t get mononucleosis were typically infected with EBV in childhood, when symptoms are less severe and similar to those of a cold.
When infecting us, EBV especially targets cells of the immune system called B-cells. In rare cases, the virus makes these cells become cancerous as it takes control of them. However, that’s not the only harm done by EBV. The virus has long been suspected of causing a whole range of autoimmune diseases, including multiple sclerosis, lupus, type 1 diabetes, rheumatoid arthritis and several others. A large-scale study of American military personnel has provided powerful proof that, at the very least, the connection of EBV to multiple sclerosis is valid. In the study, scientists found that EBV infection incurs a thirty-two-fold increased risk of developing the disease. As mentioned, this has been our suspicion for a long time, but it has been difficult to prove causation. First, because many people are infected with EBV without getting multiple sclerosis. And second, because there can be years between the initial infection and its consequences. Even fifteen years after being infected with EBV, it seems the risk of getting multiple sclerosis is still higher than normal for example.
Autoimmune diseases like multiple sclerosis are diseases where the immune system mistakenly targets the body. It might sound odd that an infection can make us do this to ourselves, but the reason is as fascinating as something horrible can be. As we’ve discussed, microbes really don’t like the immune system and try to avoid it. Just as in the jungle, the best way to hide is camouflage. Bacteria and viruses can do this by evolving proteins that look a lot like our own. Your immune system is trained to recognise what your own cells and proteins look like so that it only attacks outsiders. This means pathogens can sometimes successfully hide by pretending to be a normal part of your body. However, if such a pathogen is recognised by your immune system, big trouble might ensue. Then, your immune system can mistakenly begin to attack your own cells because it has now learned that’s what the enemy looks like. In this case and many others, the pathogen doesn’t target us directly – but it doesn’t care about us either, and so can end up causing a lot of damage in trying to reach its own goals.
Unfortunately, even though we now know a lot about the damage caused by common infections such as CMV and EBV, it is not easy to avoid either. Besides, it’s quite likely you’re already infected. However, it’s still worthwhile exercising a little caution. For instance, CMV can infect people multiple times, and due to the chronic nature of the infection, each time just makes matters worse. Besides, CMV and EBV are probably just the tip of the iceberg. Consider, for instance, that the rate of premature babies plummeted around the world during the early coronavirus lockdowns. This was a notoriously hard time for various pathogens, as we made it a lot more difficult for infections to spread. So maybe the reason for the lack of premature babies is that premature birth has an as-yet unidentified viral cause or contributor. Or consider the coronavirus itself, which seems to increase the risk of developing everything from diabetes to various heart conditions.
As a whole, there are countless viruses that target humans, including ones we don’t know about yet. It’s not hard to imagine that some of these contribute to ageing or disease; nor is it difficult to envision that diseases, for which we haven’t yet identified the cause, could turn out to have bacterial or viral involvement. Okay, it might not be particularly wise to become a paranoid hypochondriac either, but it’s certainly worthwhile using a little common sense and of course, getting vaccinated.