Involvement of Cryptosporidium parvum Cdg7_FLc_1000 RNA in the Attenuation of Intestinal Epithelial Cell Migration via Trans-Suppression of Host Cell SMPD3

Infection by Cryptosporidium parvum causes inhibition of intestinal epithelial turnover, but underlying mechanisms are unclear. This study indicates that parasite Cdg7_Flc_1000 RNA is delivered into host cells during infection, attenuating epithelial cell migration through suppression of host SMPD3....

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Veröffentlicht in:The Journal of infectious diseases 2018-01, Vol.217 (1), p.122-133
Hauptverfasser: Ming, Zhenping, Gong, Ai-Yu, Wang, Yang, Zhang, Xin-Tian, Li, Min, Mathy, Nicholas W, Strauss-Soukup, Juliane K, Chen, Xian-Ming
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Sprache:eng
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Zusammenfassung:Infection by Cryptosporidium parvum causes inhibition of intestinal epithelial turnover, but underlying mechanisms are unclear. This study indicates that parasite Cdg7_Flc_1000 RNA is delivered into host cells during infection, attenuating epithelial cell migration through suppression of host SMPD3. Abstract Intestinal infection by Cryptosporidium parvum causes inhibition of epithelial turnover, but underlying mechanisms are unclear. Previous studies demonstrate that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected epithelial cells. Using in vitro and in vivo models of intestinal cryptosporidiosis, we report here that host delivery of parasite Cdg7_FLc_1000 RNA results in inhibition of epithelial cell migration through suppression of the gene encoding sphingomyelinase 3 (SMPD3). Delivery of Cdg7_FLc_1000 into infected cells promotes the histone methyltransferase G9a–mediated H3K9 methylation in the SMPD3 locus. The DNA-binding transcriptional repressor, PR domain zinc finger protein 1, is required for the assembly of Cdg7_FLc_1000 into the G9a complex and associated with the enrichment of H3K9 methylation at the gene locus. Pathologically, nuclear transfer of Cryptosporidium parvum Cdg7_FLc_1000 RNA is involved in the attenuation of intestinal epithelial cell migration via trans-suppression of host cell SMPD3.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jix392