Widespread cold virus you've never heard of may play key role in bladder cancer

Scientists think a very common childhood infection may be linked to bladder cancer — and now, they're figuring out the chain reaction that connects the two diseases.

It's known that people who get kidney transplants are three times more likely to develop bladder cancer than the general population. Researchers have hypothesized that because transplant patients are immunosuppressed, dormant viruses lurking in the body are given the opportunity to reactivate.

These sleeping pathogens include BK virus (BKV), also called human polyomavirus type I, a common cold virus that 95% of people pick up as children. After an infection, the virus then lies dormant in the kidney. This introduces a question: Can the BK virus cause cancer years after it infects someone?

In a study published Dec. 3 in the journal Science Advances, researchers showed that the virus can cause the type of DNA damage that is also seen in bladder cancer that occurs later in life. But instead of finding DNA mutations directly caused by the virus, the researchers found that the culprit was the body's own immune system.

"This is a nicely-done laboratory study to show a possible way that BKV could have a larger role in bladder cancer than previously thought," Dr. Patrick Moore, a tumor virology researcher at the University of Pittsburgh who was not involved in the study, told Live Science in an email.

Connecting the dots

There are several types of viral infections that can lead to cancer. Some viruses, such as HPV, hijack the host cells of the infected person and insert their viral genetic material into the human genome, which causes the host cell to become cancerous. However, in some cancers, like those originating in the bladder, no detectable virus is present —but nonetheless, there are genetic signs of a previous viral infection.

"The long-running narrative since the 1950s has been that smoking and industrial exposures are the big cause of bladder cancer," said senior study author Simon Baker, a cancer researcher at the University of York in the U.K. But the patterns of DNA mutation seen in bladder cancers are different from those resulting from chemical carcinogens.

Instead, the cancers bear mutational signatures known to be caused by a family of enzymes called APOBEC. Normally, these enzymes help form the body's first-line defense against viruses and other pathogens. "They have these signatures from APOBECs, and we know APOBECs are part of the antiviral host defense," Baker explained.

Baker and his team took healthy human bladder cells and infected them with the BK virus in lab dishes. They found that the cells not only exhibited mutations similar to those seen in bladder cancer but also boosted the activity of APOBEC3, an enzyme that damages viral genomes in response to infection.

When the scientists turned off APOBEC3 and then infected the cells with the BK virus, the DNA damage didn't occur. This finding suggests that the enzyme made by the host cell was causing the damage, not the virus itself.

Additionally, the researchers found increased APOBEC3 expression and cancer-like genetic mutations in nearby "bystander" cells that hadn't been infected with the virus. So, a cell doesn't have to contain the actual virus to accumulate genetic mutations caused by an infection elsewhere in the body.

"That was a surprise," Baker said. "But the reason it makes perfect sense is that … bladder cancers don't have viruses in them." This finding starts to unravel the connection between early-life viral infections and cancers diagnosed decades later.

A starting point

Although these initial data are impactful, Moore said he would like to see whether patients with bladder cancer are infected more often with the BK virus than people without the cancer.

"It is intriguing," he said, "but only a starting point and work needs to be done to show its actual importance to human cancer."

When a person contracts the BK virus in childhood, they generally experience common cold symptoms before recovering. The virus then stays inactive, or dormant, in the kidney, bladder and tubes between the two organs. For most people, it never becomes an issue, and it's not routinely tested for outside of hospital settings.

For those about to have a kidney transplant, however, the immunosuppressants that prevent the rejection of their new kidney can also result in the reactivation of the BK virus, possibly damaging the kidneys, ureter and bladder in the process.

Tim Tavender, a kidney transplant patient from Southampton, developed a BK virus infection following his procedure and eventually had bladder cancer.

"Seeing this research makes me hopeful," Tavender told The Independent. "If scientists like Dr. Baker can find new ways to control BK virus, it could spare other people from going through what I did — and that would be life changing."