Genetically Modified Mice May Help Fight Aggressive Form of Hepatitis

Efforts to develop an effective treatment for hepatitis D virus (HDV) have long been inhibited by laboratory mice not being susceptible to the virus. To address this, researchers were able to genetically humanize mice to be persistently infected with HDV, according to a study published in Science Translational Medicine.

"To our knowledge, this is the first time the entire HDV life cycle has been recapitulated in a mouse model with inheritable susceptibility to HDV," researcher Alexander Ploss, PhD, associate professor, Princeton University, said in a press release.

HDV is the most aggressive form of viral hepatitis, affecting 20 million people worldwide who are at high risk of developing liver fibrosis, cirrhosis, and liver cancer, according to the study. There is currently no cure for HDV, although an anti-hepatitis B virus (HBV) vaccine can prevent infection, the researchers noted.

Because HDV is only able to produce a single protein on its own, it requires additional proteins provided by HBV, according to the study. Patients who already have HBV can also contract HDV or be infected simultaneously by both viruses. However, the lack of antiviral treatments for HDV leaves these patients with limited options.

Although both viruses similarly infect the liver by binding to a surface protein called NTCP, the viruses are not able to recognize the protein in mice, which prevents infection and makes it difficult to study in the laboratory, according to the study.

To overcome this challenge, the researchers generated mice with the human NTCP protein in their liver cells, which subsequently allows infection by HBV and HDV. The results showed that HDV can establish persistent infection if the HBV proteins needed to propagate are provided.

The genetically modified mice allowed the researchers to evaluate the efficacy of 2 drugs in development for HDV infection. Although both drugs were able to suppress HDV levels, either in combination or individually, they did not completely cure the mice, as viral levels rebounded within weeks following treatment, according to the study.

"This is largely in line with recently reported data from clinical trials, showing the utility of our model for preclinical antiviral drug testing," study lead Benjamin Winer, graduate student, Princeton University, concluded in the press release.