Despite its rise, hepatitis E is a disease that may be overlooked. During infection with the hepatitis E virus, random mutations often give rise to virus variants that can coexist within an infected person. The antiviral agent Ribavirin, which many chronically infected patients receive, can even increase the formation of such variants. However, post-treatment relapses have been reported often. Now, researchers at Ruhr-University Bochum in Germany analyzed chronically infected patients treated with ribavirin in the laboratory and learned how hepatitis E tricks the immune system.

The findings are published in the journal PNAS in a paper titled, “A ribavirin-induced ORF2 single-nucleotide variant produces defective hepatitis E virus particles with immune decoy function.”

“Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and is the leading cause of enterically transmitted viral hepatitis worldwide,” wrote the researchers. “Ribavirin (RBV) is currently the only treatment option for many patients; however, cases of treatment failures or posttreatment relapses have been frequently reported. RBV therapy was shown to be associated with an increase in HEV genome heterogeneity and the emergence of distinct HEV variants. In this study, we analyzed the impact of eight patient-derived open reading frame 2 (ORF2) single-nucleotide variants (SNVs), which occurred under RBV treatment, on the replication cycle and pathogenesis of HEV.”

The research team took a closer look at eight capsid protein variants from samples of chronically infected patients treated with ribavirin in the laboratory. The team sought to determine if genetic changes bring advantages or disadvantaged for the virus and if they influenced the virus’ ability to replicate or its infectivity.

While seven of the investigated mutations behaved exactly like the wild-type virus, we found differences in one mutant,” reported Toni Luise Meister, PhD, a postdoc Ruhr-University Bochum. This mutation affects the capsid protein, which is essential for packaging the viral particles.

“The viruses with this mutation are assembled incorrectly, are probably smaller than the wild-type virus, and the capsid protein does not accumulate in the cell,” described Daniel Todt, PhD, a postdoc researcher at Ruhr-University Bochum. These particles are not infectious, but are correctly recognized and bound by antibodies of the immune system. “This could be an advantage for the virus. These defective particles could potentially catch antibodies, so that there are no longer enough to neutralize correctly assembled, infectious virus particles,” speculated Eike Steinmann, PhD, director, department for molecular and medical virology, Ruhr-University Bochum.

“These findings provide insights into understanding the biology of circulating HEV variants and may guide the development of personalized antiviral strategies in the future,” concluded the researchers.