Abstract:
:Rotavirus infection has emerged as an important cause of complications in organ transplantation recipients. Immunosuppressants used to prevent alloreactivity can also interfere with virus infection, but the direct effects of the specific type of immunosuppressants on rotavirus infection are still unclear. Here we profiled the effects of different immunosuppressants on rotavirus using a 2D culture model of Caco2 human intestinal cell line and a 3D model of human primary intestinal organoids inoculated with laboratory and patient-derived rotavirus strains. We found that the responsiveness of rotavirus to Cyclosporine A treatment was moderate and strictly regulated in an opposite direction by its cellular targets cyclophilin A and B. Treatment with mycophenolic acid (MPA) resulted in a 99% inhibition of viral RNA production at the clinically relevant concentration (10 μg/ml) in Caco2 cells. This effect was further confirmed in organoids. Importantly, continuous treatment with MPA for 30 passages did not attenuate its antiviral potency, indicating a high barrier to drug resistance development. Mechanistically, the antiviral effects of MPA act via inhibiting the IMPDH enzyme and resulting in guanosine nucleotide depletion. Thus for transplantation patients at risk for rotavirus infection, the choice of MPA as an immunosuppressive agent appears rational.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Yin Y,Wang Y,Dang W,Xu L,Su J,Zhou X,Wang W,Felczak K,van der Laan LJ,Pankiewicz KW,van der Eijk AA,Bijvelds M,Sprengers D,de Jonge H,Koopmans MP,Metselaar HJ,Peppelenbosch MP,Pan Qdoi
10.1016/j.antiviral.2016.07.017subject
Has Abstractpub_date
2016-09-01 00:00:00pages
41-9eissn
0166-3542issn
1872-9096pii
S0166-3542(16)30109-7journal_volume
133pub_type
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