Hepatitis E virus (HEV) is estimated to cause more than 56 thousand deaths each year, and although most infections remain asymptomatic, HEV is still considered one of the most common causes of acute viral hepatitis and is an ongoing concern for immunosuppressed transplant patients. Additionally, because HEV is a feco-orally transmitted virus, it is also known to spread rapidly in developing countries where clean water sources are scarce. Until recently, the development of promising antiviral therapies and treatment options for chronic HEV has been hindered by the lack of a robust and convenient animal models. However, according to a recent study published in the journal Disease Models & Mechanisms by Debing, et al, it appears as though athymic nude rats infected with the rat HEV strain LA-B350 may be just the models researchers have been looking for. Furthermore, because the rat HEV virus shares about a 60% sequence identity with human HEV, including “several highly conserved motifs in key viral genes,” the authors propose that rat HEV is a suitable model for the human version of hepatitis E.
In this study, athymic nude rats showed susceptibility to rat HEV, which ultimately led to a chronic infection. This closely resembles the situation observed in immunocompromised patients who frequently also develop chronic HEV. Additionally, these LA-B350 infected rats were determined to be a useful model for in vivo antiviral studies, as the human drug ribavirin was shown to effectively promote virus shedding in the feces of treated rat HEV models.
Though further study is certainly required, Debing, et al have also shown that the humanization of the RdPp protein is possible, thereby improving the potential of the rat model. The ability to effectively replace certain sequences and/or motifs of rat HEV with their counterparts from the human HEV strains ultimately opens a door for even better rat models for HEV in the future.