PNAS: A new HBV virus-causing chronic infections in horses worldwide

PNAS: A new HBV virus-causing chronic infections in horses worldwide.  EqHBV can naturally infect different types of horses and mimic the infection pattern of HBV.

Preclinical trials of new treatments for chronic hepatitis B require suitable animal models. Due to the lack of suitable preclinical animal models, the development of chronic hepatitis B drugs has been hindered. Traditional animal models include chimpanzees, tree shrews and groundhogs. However, due to ethical issues, experimental HBV infection of chimpanzees is limited. The HBV infection rate of tree shrews is low, and the primary tree shrew hepatitis virus is unclear. HBV can cause chronic infection of woodchucks, but the hibernation of woodchucks affects the infection process and complicates the experimental device. Humanized chimeric mice can be infected with HBV, but due to immunodeficiency, they are generally not suitable for research on new drug candidates.

The newly discovered animal homologues of human viruses may provide new in vivo models, such as new hepatitis C infection models based on HCV-related viruses from rats and horses. Recently, a variety of viruses related to hepatitis B virus have been discovered in various animals such as bats and shrews. However, their potential availability as an animal model for chronic hepatitis B is unclear because of the challenges of keeping these animals, their short life spans and unclear infection patterns.

Because horses and donkeys carry the closest known HCV homologs, and because of similar transmission routes, human HBV/HCV co-infection is also common. The research team from Germany recently published the latest research results in PNAS. It investigated the HBV homologues of horses sampled around the world and described a ubiquitous new hepatitis B virus that infects donkeys and zebras. Chronic infection of hepatitis B.

Research methods and results

The author performed HBV screening on 2,917 specimens of horses from five continents. A unique HBV (equine HBV, EqHBV) was found in 3.2% of donkeys and zebras, and antibodies to EqHBV were found in 5.4% of donkeys and zebras.

A. Genome of HBV and EqHBV; B. Maximum likelihood phylogeny based on whole genome

Molecular, histopathological and biochemical analysis showed that the infection pattern of EqHBV is similar to that of human HBV, including hepatotropic, moderate liver damage, evolutionary stagnation, and potential horizontal transmission of the virus.

Hepatophilicity and pathogenicity of EqHBV: A. Concentration of EqHBV in Ghanaian donkey samples; B&C. Histopathological analysis of donkey liver

Naturally infected donkeys show chronic infection similar to chronic hepatitis B, with a serum viral load of up to 2.6 × 109 copies/mL, lasting for more than 6 months, and a weak antibody response. Equine HCV antibodies were also detected in 26.5% serum EqHBV positive donkeys, confirming the susceptibility to these two hepatitis viruses. Pseudoviruses carrying the surface protein of EqHBV cannot infect human cells through the HBV receptor NTCP (Na+/taurocholic acid cotransport peptide), suggesting an alternative virus entry mechanism. Both HBV and EqHBV pseudotypes can infect primary horse hepatocytes in vitro, indicating that EqHBV has a wide host range in horses, and suggesting that horses may be suitable for EqHBV and HBV infection in vivo. Evolutionary analysis shows that EqHBV originated in Africa thousands of years ago, and is as domesticated as donkeys.

In general, EqHBV can naturally infect different types of horses and mimic the infection pattern of HBV. Equine animals provide a unique opportunity for preclinical testing of new treatments for chronic hepatitis B and for studying the interaction of HBV/HCV co-infection.

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