Through the use of a large battery of experiments employing a variety of methodologies, Yin et al made several important discoveries regarding the mechanisms of rotavirus immunosuppression. For example, they demonstrated that glucocorticosteroids and FK506 did not affect rotavirus replication. Additionally, study results revealed that the cellular targets of CsA, CypA and CypB, inhibited and promoted rotavirus replication, respectively, and collectively determined responsiveness to CsA. MPA was also found to be a potent inhibitor of rotavirus replication in both SA11 and patient-derived rotavirus strains in cell line and organoid models through depletion of the cellular guanosine nucleotide pool. Lastly, MPA was shown to have a high barrier to the development of drug resistance.
In discussing the results generated from the experiments conducted in their study, Yin et al said that, "... by profiling different immunosuppressants, we have found that the responsiveness of rotavirus to CsA treatment is largely determined by the relative expression levels of its cellular targets, CypA and CypB. Importantly, we have identified MPA as a potent inhibitor of rotavirus infection with a high barrier to resistance development. It acts via the inhibition of the IMPDH enzymes to deplete cellular nucleotide to restrict rotavirus infection."
Regarding the broader implications of the study’s results, Yin et al stated, "... understanding the distinct effects and their mode-of-actions of different immunosuppressants on rotavirus infection bears important implications for transplant clinicians to design optimal protocols of immunosuppression for infected organ recipients." Furthermore, the authors noted that, "Understanding such direct effects on rotavirus by different immunosuppressive agents is certainly relevant to the management of infected transplantation patients, as well as to the development of potential new antivirals."
William Perlman, PhD, CMPP is a former research scientist currently working as a medical/scientific content development specialist. He earned his BA in Psychology from Johns Hopkins University, his PhD in Neuroscience at UCLA, and completed three years of postdoctoral fellowship in the Neuropathology Section of the Clinical Brain Disorders Branch of the National Institute of Mental Health.
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