Saturday, June 18, 2011

Discovery of Hepatitis C Virus in Canines Opens New Doors for Research on Deadly Human Pathogen

Recent research from the Center for Infection and Immunity (CII) at Columbia University’s Mailman School of Public Health, the University of Edinburgh, and the Center for the Study of Hepatitis C and Pfizer Veterinary Medicine reports the discovery of a hepatitis C-like virus in dogs. The identification and characterization of this virus gives scientists new insights on how hepatitis C in humans may have evolved and possible a model system to study how it causes disease.

Human hepatitis C virus (HCV) affects approximately 200 million people worldwide. According to the Centers for Disease Control and Prevention (CDC), 3.2 million people in the United States are chronically infected. The majority of these patients do not even know that they are carrying the virus. This serves as a source of infection for others. ( HCV causes liver disease, fibrosis, cirrhosis, and liver cancer. HCV is most often transmitted following large or repeated exposure to infected blood. Persons who use injections drugs, are HIV-positive, or are children of infected mothers have the highest risk of infection.

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. Before researchers thought 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.

Using a sequencing platform provided by Roche 454 Life Sciences and state-of-the-art molecular techniques, Dr. Kapoor determined that like HCV, CHV’s genome contained RNA secondary structures called GORS that allow viruses to chronically infect their natural hosts. The sequence of genes that encode proteins involved in virus infection and replication were very similar between HCV and CHV. ( 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.

The discovery of canine hepatitis C (CHV) is the first known instance of hepatitis-like infection in non-human primates and suggests that the virus may have been introduced into human populations through contact with dogs or some other related species more than 500 years ago.

Viral zoonoses, infections that are transmitted from animals to humans, account for about 70% of fuman emerging infectious diseases. Although transmission between species is uncommon, sustained contact over time can increase the likelihood that a virus adapted to infect humans will evolve. Whether humans and dogs were independently infected with an ancestral virus by another species, or whether dogs infected humans, or vice verse, cannot be determined from this study.

Until recently, studies into how hepatitis C causes disease in humans have been limited by lack of animal and cell culture models. The identification and characterization of CHV allows the beginning of a new animal model for hepatitis C. This provides new tools for understanding how this virus causes disease and will facilitate drug and vaccine research and development.


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