Trapped in your DNA, and that of all mammals, is the molecular wreckage of ancient viral invaders that once plagued our ancestors. It has long been assumed that these "endogenous retroviruses" (ERVs) in our genome were either meaningless genetic debris from humanity's ancient pandemics or that viral genes had been domesticated and rendered benign, or even beneficial, by evolution.
But UC Davis Medical Center Assistant Adjunct Professor of Surgery Kiho Cho doesn't believe ERVs are always harmless. They can be dangerous, he believes—and may just be the key to a new generation of treatments for patients with afflictions as diverse as burn traumas, autoimmune disease and cancer.
A little understood tragedy of burn trauma is that many patients survive an automobile crash or house fire, only to die days or weeks later from multiple organ failure. Their livers, kidneys and lungs simply quit.
"Some burn patients survive while others—people the same age, race, sex and with similar trauma—are unable to survive," Cho said. "But why do organs fail when the injury is to the outside of the body?"
"If burns activate ERVs that suppress the immune system and contribute to organ failure, we may be able to use anti-retroviral drugs developed for AIDS, to save many burn patients."
— Kiho Cho, Manager of the Burn Research Facility
Many scientists believe that complex chemical signals are involved—molecular cascades triggered by burns that somehow overwhelm internal organs. Four years ago, Cho joined the search for those signals, in mice. His team discovered several genes that were activated in the liver after skin burns. But one gene stood out as particularly intriguing.
"We found an endogenous retrovirus sequence, structurally very similar to the ‘mouse AIDS' virus—an immunosuppressing virus," Cho explained. Burns on the skin somehow activated this ancient viral gene in the liver.
If similar ERVs reacted that way in other organs, Cho realized, they could overwhelm burn patients' immune system in major organs. And that could explain why some patients survive burns that kill others. Patients who survive, he hypothesizes, may have different ERV profiles in their genome than those who are killed by similar trauma. More importantly, if ERVs play a central role in burn mortality, there may be an unexpected way to save many patients.
"If burns activate ERVs that suppress the immune system and contribute to organ failure," he explained, "we may be able to use anti-retroviral drugs developed for AIDS, to save many burn patients."
Since that initial discovery of a burn-activated ERV in the mouse liver, Cho's team has discovered ERVs in other organs—and as predicted, they behave similarly after burn trauma.
The medical implications may extend well beyond the treatment of burn victims. Recent studies in Canada, England and the University of Kentucky show that activated ERVs produce toxic proteins in the brains of multiple sclerosis patients, killing neurons and hastening the deadly progression of the disease.
Activated ERVs have also been identified in the brains of schizophrenics. If Cho's research leads to a new paradigm in the understanding and treatment of burn victims, he hopes, it may also one day soon shed new light on how we can confront cancer, autoimmune disease and perhaps even mental illness.
— Bryant Furlow