June 19, 2018

New Virus in Capuchin Monkeys: Animal Model for Chronic HBV?

The discovery of a new hepatitis B virus in capuchin monkeys could be important in guiding future work to investigate the pathogenesis of HBV infection and potential cures for its chronic infection.
By Nicola M. Parry, BVSc, MRCVS, MSc, DACVP, ELS
“The identification of a novel primate hepadnavirus offers new perspectives for urgently needed animal models of chronic hepatitis B,” wrote Breno Frederico de Carvalho Dominguez Souza, from the University of Bonn Medical Centre in Germany, and colleagues, in a recent study published in the Journal of Hepatology.

According to the authors, hepatitis B virus (HBV) commonly infects humans. Chronic infection can have serious complications, including cirrhosis and liver cancer, which cause at least 680,000 deaths worldwide each year.

Chronic HBV thus remains a major public health issue with no effective cure. And, despite recent advances in understanding HBV infection, research to investigate potential cures remain stalled by the lack of suitable animal models for chronic HBV infection.

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HBV, which belongs to the genus Orthohepadnavirus in the family Hepadnaviridae, is divided into 10 genotypes (A-J) in humans. And, while additional genotypes infect Old World monkeys such as chimpanzees, gorillas, orangutans, and gibbons, no evidence exists to suggest that these monkey genotypes can infect humans.

In addition to HBV, woolly monkey HBV is the only other hepadnavirus known to infect nonhuman primates, and only a paucity of data exist on HBV in New World species.

With this in mind, Souza and colleagues conducted a study in which they screened New World monkeys in Brazil for hepadnaviruses.

Using molecular and serologic tests, they screened sera from 124 New World monkeys belonging to at least 10 different species. Most of the animals screened were capuchin monkeys (N = 95).

In their study, Souza and colleagues identified a new species of HBV in capuchin monkeys, which they named capuchin monkey HBV (CMHBV). “We found CMHBV-specific antibodies in five animals and high CMHBV concentrations in one animal,” they wrote.

According to the researchers, the 5 monkeys that were antibody positive appeared healthy. One other monkey tested positive for hepadnavirus DNA by polymerase chain reaction assay. This animal was thin, lethargic, and mildly dehydrated, they noted, and died 6 months after sampling. However, because no additional samples were provided after the monkey’s death, the researchers were unable to determine whether its clinical signs were related to CMHBV infection.

Nevertheless, the virus in this case had an intact preCore domain, the authors noted. This domain is responsible for production of hepadnaviral e-antigen, which is a key viral protein involved in establishing chronic HBV infection. As a consequence, the researchers hypothesized the existence of chronic infection in the hepadnavirus DNA-positive monkey. And, if CMHBV can cause chronic infection, CMHBV-infected animals could serve as new animal models for chronic HBV infection in humans, they said.

In the laboratory, the researchers found that the new virus produced infection patterns similar to those of HBV. It also infected human liver cells using the same receptor that HBV uses, leading the authors to suggest a zoonotic potential for hepadnaviruses circulating in New World monkeys.

“However, infection experiments relying on full hepadnaviruses and primary human liver cells will be required to permit definite conclusions on the zoonotic potential of CMHBV,” they stressed.

And, when they performed evolutionary analyses on CMHBV, Souza and colleagues found information that helped to explain the general evolution of hepadnaviruses in primates. Their findings suggested that primates began carrying hepadnaviruses millions of years ago. In particular, the origins of HBV-related viruses may date back to African ancestors of New World monkeys at that time, they said, when these animals entered South America during its transatlantic colonization.

The researchers also found a link between HBV and hominoid ancestors, including humans and apes, leading them to suggest that the origins of HBV date back to before modern humans even evolved.

“Our results elucidate the evolutionary origins and dispersal of primate HBV, identify a new orthohepadnavirus reservoir, and enable new perspectives for animal models of hepatitis B,” Souza and colleagues concluded.

 
Dr. Parry, a board-certified veterinary pathologist, graduated from the University of Liverpool in 1997. After 13 years in academia, she founded Midwest Veterinary Pathology, LLC, where she now works as a private consultant. Dr. Parry writes regularly for veterinary organizations and publications.

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