Viral Outbreaks in Dogs Yield Clues on Origins of Hepatitis C

By CARL ZIMMER

Hepatitis C is, in some ways, a high-profile disease. Worldwide, an estimated 200 million people are infected with the virus. Some of them will suffer cirrhosis, liver cancer and even death. Celebrities like Steven Tyler of Aerosmith and “American Idol” have spoken publicly of their infections. 

But mysteries still shroud the disease. Typically spread through drug injections, blood transfusions and sexual contact, hepatitis C can quietly cause liver damage for 20 years or more before victims become aware that they are ill. “Worldwide, it’s causing devastation,” said Brian Edlin, an epidemiologist at SUNY Downstate Medical Center in Brooklyn.

Its origins are even more puzzling. Hepatitis C is a distinct disease from hepatitis A and B; it belongs to an entirely different virus family that includes diseases like West Nile fever and yellow fever. Scientists have searched for years for related viruses in animals to figure out how it evolved into a human disease.

“Identifying the species reservoir of hepatitis C — one of the most common and deadly of all human viruses — has been something of a holy grail in studies of viral evolution,” said Eddie Holmes, a virologist at Penn State University.

Now scientists have gotten an important clue, finding a close relative in an unexpected host: dogs.

The discovery, published in Proceedings of the National Academy of Sciences, “represents a major step forward,” said Dr. Holmes, who was not involved in the research.

The finding came as a surprise to all the scientists involved. Researchers at Pfizer were investigating virus outbreaks in dogs in shelters across the United States. They swabbed the noses of dogs sick with respiratory diseases and searched for viruses. In some cases they could not isolate a known virus, so they sent samples to the Center for Infection and Immunity at Columbia University, where researchers specialize in finding new viruses.

The Columbia center found that six of nine dogs in one outbreak and three of five in another shared the same unknown virus. Nasal swabs from 60 healthy dogs showed no sign of it.

Amit Kapoor, a Columbia virologist, compared the genetic material of the new virus to known ones. His analysis revealed it was closely related to the hepatitis C virus (HCV for short). “I was not expecting anything like HCV,” Dr. Kapoor said. Like many other researchers, he assumed that it had evolved from a primate virus, because chimpanzees can be experimentally infected with hepatitis C.

But as Dr. Kapoor and Peter Simmonds of the University of Edinburgh analyzed more genetic data, the link continued to hold. Dr. Kapoor and his colleagues have called the new virus canine hepacivirus, or CHV for short.

The Columbia researchers collaborated with hepatitis C experts at Rockefeller University in New York to compare the two viruses. Canine hepacivirus infects the airways of dogs and is present at low levels in the liver.

Based on the genetic similarity of the two viruses, the scientists estimate that they share a common ancestor that lived 500 to 1,000 years ago. “It’s really quite rough,” said W. Ian Lipkin, the director of the Center for Infection and Immunity and an author of the journal article. “This is not something that happened recently, but it didn’t happen hundreds of thousands of years ago.”

The researchers see three possibilities for the origin of the viruses. The least likely is that dogs acquired hepatitis C from humans. Another possibility is that dogs and humans both acquired the virus from an unknown animal. This is the sort of evolution that gave rise to the 2004 outbreak of SARS. At first scientists found the virus in the catlike palm civet of Southeast Asia. But later research revealed that the virus actually started out in bats and then spread to palm civets and humans.

A third possibility — one favored by Dr. Kapoor — is that the virus started in dogs, and then evolved into a liver-infecting disease in humans.

“The evidence we have favors an origin in dogs,” Dr. Kapoor said.

To test these alternatives, Dr. Kapoor and his colleagues plan to search for hepatitis C-like viruses in dogs from other countries, as well as in foxes and other species of carnivorous mammals.

Even before that mystery is resolved, however, researchers expect to see some benefits from the discovery of canine hepacivirus. In the current issue of the journal Nature, Dr. Edlin argues that much more needs to be done to fight the hepatitis C epidemic. Along with better surveillance, he sees a need for research into antiviral drugs as well as vaccines. (Currently there is no commercially available hepatitis C vaccine.) Researchers may now be able to study CHV in dogs to get insights into hepatitis C in humans.

“I’m sure this will be helpful,” Dr. Edlin said.