Study after study is implicating viruses, some symptomless, in long-term, even fatal, illnesses. Do all infections contribute to chronic disease? Not necessarily. But, says Nikhil Dhurandhar, an associate professor in the department of infections and obesity at Pennington Biomedical Research Center at Louisiana State University, “They should be given serious thought as contributors.”
Viruses: hard to eradicate
Viruses by their nature are very tenacious. “Once inside a cell, they are tough to get rid of,” explains Bhagirath Singh, scientific director of the Institute of Infection and Immunity, one of the Canadian Institutes of Health Research (CIHR), in London, Ont. “They have a propensity to stay in your system and cause long-term chronic diseases.” We already knew the chicken pox virus can stay in the body for a lifetime and crop up as shingles many decades after the spots have disappeared, for instance. But new studies have revealed that adenovirus-36, a symptomless virus found in the gut, may later trigger obesity, while coxsackie viruses—which cause the common cold—can contribute to heart disease. As Vancouver immunologist Marc Horwitz puts it: “One person’s cold might be your nightmare.”
People can “catch” viruses when body fluids or fecal material from those who are infected enter their respiratory or gastro-intestinal tract—via sneezing, dirty toilet seats, kissing or germy doorknobs. But if scientists could figure out how to prevent viruses from getting into our cells in the first place, they could make a dent in the number of people getting sick. Help may come in the form of new vaccines, as well as drugs that help our bodies fight the virus or stop it from creating a chronic illness.
Victory over HPV
One of the few cases where research has completed a full circle—from identifying a viral disease trigger to preventing the disease—is with human papillomavirus (HPV), a common sexually transmitted virus. As with many viruses, people often don’t even know they have it. It is known that HPV causes most cervical cancers. Now there is an effective vaccine available—Gardasil is approved in Canada for females age nine to 26—that protects against the HPV types associated with genital warts and about 70 percent of cervical cancers.
New virus-blocking drugs are on the horizon as well. In a brand new study, Canadian researchers found a way to knock out two “bad” proteins in mice and thereby render the animals resistant to viral infections, explains Mauro Costa-Mattioli, a co-author of the study and a biochemist at McGill University and the McGill Cancer Centre. The proteins, called 4E-BP1 and 4E-BP2, repressed interferon—the body’s first line of defence against viral infection. Once the proteins were put out of action, interferon could do its job, preventing the virus from reproducing. Costa-Mattioli says he suspects that drugs to inactivate these proteins in humans—and thereby protect against some viruses—should be available in about a decade.
Of course, the first step in developing vaccines or blocking drugs is to identify which viruses are associated with what chronic illnesses, and determine how those viruses do their dirty work. Here is a snapshot of some of the latest findings.
It has been known for decades that coxsackie viruses and adenoviruses (which cause colds and stomach upset, respectively), and parvoviruses (which cause fifth disease, a very common rash in children) can, in some cases, travel to the heart and cause inflammation. Although these viruses are usually cleared from the body within a week or two, recent studies have shown how often they stick around. “In all comers with heart failure, about one in eight has a virus as the cause,” says Dr. Peter Liu, scientific director of the CIHR’s Institute of Circulatory and Respiratory Health in Toronto. In people under 30, it is one in three.
While studying how the coxsackie virus interacts with the immune system to cause heart disease, scientists recently discovered a paradox: The more the immune system is activated to resist the virus, the more the virus multiplies. Once it enters the body, the immune system tries to defend against it by producing white blood cells. But those cells can actually help the virus. “The virus travels in the body and targets the heart by riding with the white blood cells,” says Liu. “This has been nicknamed the Trojan Horse scenario.” Understanding mechanisms such as this brings researchers closer to developing vaccines to target adenoviruses, coxsackie viruses, parvoviruses and others that can trigger heart disease. It is already known that people who have heart disease can reduce the risk of a heart attack by getting a flu vaccine. New vaccines will take at least four or five years before they go to clinical trials, Liu estimates.
Autoimmune diseases are serious, usually chronic, illnesses in which the immune system is overactivated and attacks the body’s own cells. Examples include multiple sclerosis, rheumatoid arthritis, lupus and type 1 diabetes. Although these diseases have many different causes, both genetic and environmental, viruses have been implicated as important triggers. For instance, clinical and epidemiological evidence has linked multiple sclerosis with coronavirus, Epstein-Barr virus (EBV), herpes virus 6, JC virus and rubella; rheumatoid arthritis with EBV and parvoviruses; lupus with cytomegalovirus, EBV and parvoviruses; and type 1 diabetes with rubella, enteroviruses, mumps, rotavirus, cytomegalovirus, coxsackie virus and parvoviruses. “I am more and more in awe of the power of viruses,” says Horwitz, who studies these links in the division of microbiology and immunology at the Life Sciences Centre at the University of British Columbia.
TYPE 1 DIABETES A recent study by Horwitz and colleagues found that when a protein called TGF-beta was given to mice with coxsackie virus, it protected them from developing type 1 diabetes without suppressing the immune system’s reaction to the virus. “This is really exciting to us,” says Horwitz, who hopes that TGF-beta or something similar could prevent the virus from inducing autoimmune disease in humans. He estimates that in the next five to 10 years, drugs will be available that suppress the autoimmune response, while allowing our bodies to fight off the virus.
MULTIPLE SCLEROSIS EBV, a type of herpes virus known to cause mononucleosis (or kissing disease, because it is passed through saliva), may be the culprit in many cases of multiple sclerosis (MS). A recent study showed the strength of that link. “Individuals infected with EBV are about 10 times more likely to develop MS than those not infected,” notes Dr. Alberto Ascherio, an associate professor of nutrition and epidemiology at the Harvard School of Public Health. “Evidence suggests that if EBV infection could be prevented, the majority of MS cases would also be prevented.” He explains that scientists are still trying to figure out the mechanism that links EBV and MS, and are working on a vaccine against EBV.
Research has been accumulating since 1982 that several viruses can cause obesity in animals, and new research indicates this is the case in humans, too. Nikhil Dhurandhar, of the Pennington Biomedical Research Center at Louisiana State University, and his colleagues published a landmark paper showing that people who have had adenovirus-36 (Ad-36) are more likely to be obese than those who have never had it. “I call it infectobesity, or obesity of infectious origin. Clearly not all obesity is due to infections, but one of the causes could be infections,” says Dhurandhar, who admits the concept is still controversial. How else can we explain the huge differences between people’s caloric requirements, he asks? There is so much that is not known in terms of genetic, biological and biochemical influences, he says, and several groups of researchers around the world are focusing on the virus-obesity link. He estimates a vaccine to block Ad-36 may be available in five to 10 years.
How can a virus cause cancer? CIHR’s Bhagirath Singh explains: The virus enters the cell, forces its own machinery into the cell, mutates the cell and causes the cell to grow uncontrollably. “Whether or not this happens and how long it takes depends on many things, including genetic makeup, ethnicity and age.” The best-known example of a virus-cancer link is HPV, which causes cervical cancer. Some other cancers are linked to viruses. Infection with EBV is associated with a higher risk of getting nasopharyngeal cancer and some types of fast-growing lymphomas, and possibly stomach cancer. Hepatitis B and C viruses can increase a person’s susceptibility to liver cancer because they can cause chronic infection in the liver. And while HIV does not appear to cause cancer directly, it can render the body less able to fight off infections such as HPV, which in turn can lead to cancer. Vaccines are available to fight hepatitis B and HPV.
Reducing your virus risk
While we await the development of vaccines and new medications, there are some measures each of us can take to reduce the chances of getting sick. Most viruses, says Singh, are spread either through direct contact or through body fluids. His biggest piece of advice is one we’ve all heard before: “Wash your hands with soap after any activity that may expose you to body fluids or droplets.” He also recommends practising safe sex to decrease your chances of acquiring sexually transmitted viruses, and avoiding exposure to HIV, hepatitis or the flu. Eating well, exercising regularly and getting enough sleep will give your body more strength to fight common bugs floating around, he adds.
If you do get a virus, it is very important to stay home and rest, Liu says. Studies have shown that one of the places where the common cold virus can travel is to the heart. “When you have an illness, you should rest. Your heart muscle may be weakened. Allow nature to do its healing job. You don’t want your condition to linger.”
Viruses have always been difficult to contain. The true potential to avoid or minimize chronic disease by preventing or treating infections may yet be substantially underestimated, according to researchers at the Centers for Disease Control and Prevention. But, clearly, we humans are arming ourselves with the knowledge we’ll need to begin to outsmart them now and in the future.