Based on 2D and 3D in vitro models, treatment with mycophenolic acid (MPA), an inhibitor of the type II isoform of inosine monophosphate dehydrogenase (IMPDH), confers very high levels of drug resistant rotavirus viral replication suppression and may therefore be a useful immunosuppressive agent for preventing rotavirus infection in transplantation patients, according to the results of a study published recently in Antiviral Research1
Following organ transplantation, immunosuppressant drugs are administered as a matter of routine in order to prevent graft rejection. Unfortunately, immunosuppression in general increases susceptibility to infection
with rotavirus, a leading cause of gastroenteritis. At present, only the calcineurin inhibitor cyclosporine A has been shown to inhibit rotavirus replication in experimental models.2
The direct effects of other types of immunosuppressants on rotavirus infection have not been elucidated to date.
First author Yuebang Yin, Msc, a PhD student in the Department of Gastroenterology and Hepatology at the Erasmus MC-University Medical Center in Rotterdam, and his colleagues addressed this unexplored topic. The stated objectives of the study were, "... to comprehensively profile the effects and mode-of-action of different types of immunosuppressants on rotavirus including corticosteroids (prednisolone [Pred] and dexamethasone [Dex]), calcineurin inhibitors (CsA and tacrolimus [FK506]) and selective antiproliferative agents (e.g., MPA)." Furthermore, Yin et al explained that, "In vitro cell culture systems that do not contain immune cells are the ideal models for studying such direct effects of immunosuppressants on viral replication."
To accomplish their stated goals, Yin et al used a 2D culture model of the Caco2 human intestinal cell line. Because these, "... convenient and valid model systems do not capture the dynamics and architectures of the intestinal epithelium," additional experiments were also conducted using a 3D model of human primary intestinal organoids inoculated with laboratory and patient-derived rotavirus strains. These 3D cultures are regarded as capable of reproducing the in vivo tissue architecture of the intestinal epithelium,3
and had been developed previously by this research group for modeling rotavirus infection.4
According to the authors, the intended use of these 3D primary organoid cultures in this study was to validate findings obtained from the 2D system.