Did Hepatitis A Originate in Humans? Probably Not, Say Scientists

Bats are old mammals on the evolutionary scale. They are extremely important ecologically and are under stringent species protection. They often live in large colonies and form reservoirs for various viruses. [Marco Tschapka/University of Ulm]

Understanding the origins of viral pathogens allows researchers to study the underlying mechanisms that make a particular disease preferentially virulent over the multitude of other innocuous viruses. For many years hepatitis A infections, which can trigger acute liver infections, were widely considered to be the result of a pathogen of purely human and nonhuman primate origin.

However now, an international team of scientists lead by researchers at the University of Bonn has conducted a large-scale study of nearly 16,000 specimens collected from small animals across the globe and uncovered that the hepatitis A virus (HAV)—much like HIV and Ebola—can likely trace its origin to other small mammals.

“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,” explained co-author Stanley Lemon, M.D., professor of medicine at the University of North Carolina School of Medicine and 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 findings from this study were published online recently in PNAS through an article entitled “Evolutionary origins of hepatitis A virus in small mammals.”

“The seemingly purely human virus is thus most likely of animal origin,” remarked lead author Jan Felix Drexler, M.D., professor at the Institute of Virology within the University of Bonn Medical Centre and the German Centre for Infection Research (DZIF). “The study enables new perspectives for risk assessments of emerging viruses by investigating functional, ecologic, and pathogenic patterns instead of phylogeny only.”

Infections with hepatitis A virus can often trigger acute inflammation of the liver, which interestingly does not typically cause any symptoms in children and resolves without major complications. “In tropical regions, nearly all young children are infected with the hepatitis A virus and from that time on, they are immune to this disease,” noted Dr. Drexler. However, in contrast, adults infected with HAV can have much more serious symptoms and even fatal outcomes. 

In their search for the evolutionary origins of this pathogen, the researchers managed to obtain an extraordinary number of samples from an array of animal species.

“We conducted a targeted search for hepatoviruses in 15,987 specimens collected from 209 small mammal species globally and discovered highly diversified viruses in bats, rodents, hedgehogs, and shrews, which by pairwise sequence distance comprise 13 novel Hepatovirus species,” stated the researchers. “Near-complete genomes from nine of these species show conservation of unique hepatovirus features.”

Interestingly, the investigators found evidence that may hint at how a virus like HAV might have come to infect small mammals in the first place, as their data pointed to a distant ancestry of HAV in primordial insect viruses.

“It is possible that insect viruses infected insect-eating small mammals millions of years ago and that these viruses then developed into the precursors of the hepatitis A virus,” stated Dr. Drexler.

In addition to the data that the researchers uncovered, they postulated the important hypothesis that small mammals were critical for the preservation and evolution of the HAV. “Otherwise the HAV would actually have gone extinct long ago in small human populations due to the lifelong immunity of the persons once infected with it,” Dr. Drexler reasoned. “However, patients need not fear that they could contract a hepatitis A virus infection through bats or hedgehogs. It has likely been a very long time since humans first contracted the hepatitis A precursor virus from animals—moreover, such incidents are very rare.”

Beyond the evolutionary origins of HAV, this study highlights the value of analyzing animal reservoirs for determining the threat of emerging viruses to the human population.

“Our study exemplifies the utility of looking beyond phylogenetic criteria alone when conducting a risk assessment for emerging RNA viruses and the need to include functional, ecologic, and pathogenic analyses of animal reservoirs,” concluded Dr. Drexler. “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.”