Study provides novel insight into the evolution of hepatitis A virus and how it spreads to humans

Researchers at the University of North Carolina at Chapel Hill (UNC-Chapel Hill) are part of an international team led by the University of Bonn, Germany, who have found a link between the origin of hepatitis A virus (HAV) and small mammals. With the emergence of Ebola virus from bats and hantaviruses from rodents, investigators say identifying the other species infected with HAV provides novel insight into the evolution of HAV and how it spread to humans, and highlights the utility of analyzing animal reservoirs for risk assessment of emerging viruses.

"Prior to this study, we had no understanding of the origins of HAV, an ancient and common threat to health in many regions of the world", says Stanley M. Lemon, M.D., one of the study's authors and a professor of medicine at UNC's School of Medicine and UNC's Institute for Global Health & Infectious Diseases (IGHID). "Now we know that it evolved among small mammals such as bats, and spread from them to humans in the distant past." The paper "Evolutionary origins of hepatitis A virus in small mammals" was published in the Proceedings of the National Academy of Sciences (PNAS) in early November.

Hepatitis A virus causes vomiting, fatigue, fever, jaundice and inflammation of the liver. The virus is excreted in feces and can survive in the environment for prolonged periods of time. In the United States, HAV is typically acquired by ingestion of feces-contaminated food or water, as was the case in a 2013 outbreak of contaminated pomegranates in the southwestern US and Hawaii. Infection can also result from close personal contact with an infected household member or sex partner.

An HAV vaccine was developed in 1995 and has drastically reduced the number of cases of HAV in the US and many other countries. However, in developing countries in Africa, South America, Asia and the Middle East, vaccine use is limited and the spread of HAV is greatly facilitated by poor sanitary conditions. In fact, the World Health Organization (WHO) estimates in countries where HAV is endemic, all children are infected with HAV before the age of 9.

As part of a consortium of investigators, Lemon and colleagues at the University of Bonn in Germany and several international collaborators discovered that closely related HAV-like viruses exist in bats, rodents, hedgehogs and shrews by testing 15,987 samples collected from 209 diverse mammal species globally.

"Our study exemplifies the utility of looking beyond phylogenetic criteria alone when conducting risk assessment for emerging RNA viruses and the need to include functional, ecologic, and pathogenic analyses of animal reservoirs," says Jan Felix Drexler, M.D., the study's corresponding author and a professor of medicine at the Institute of Virology at the University of Bonn Medical Centre in Germany. "Next steps may include efforts to grow these viruses in cell culture and functional analyses to assess their risk of being transmitted to primate hosts."