Wang Yang, Gong Ai-Yu, Ma Shibin, Chen Xiqiang, Li Yan, Su Chun-Jen, Norall Dana, Chen Jing, Strauss-Soukup Juliane K, Chen Xian-Ming
Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA.
Department of Chemistry, Creighton University College of Arts and Sciences, Omaha, Nebraska, USA.
J Infect Dis. 2017 Feb 15;215(4):636-643. doi: 10.1093/infdis/jiw607.
Cryptosporidium parvum is an important opportunistic parasite pathogen for immunocompromised individuals and a common cause of diarrhea in young children. Previous studies have identified a panel of RNA transcripts of very low protein-coding potential in C. parvum. Using an in vitro model of human intestinal cryptosporidiosis, we report here that some of these C. parvum RNA transcripts were selectively delivered into the nuclei of host epithelial cells during C. parvum infection. Nuclear delivery of several such parasitic RNAs, including Cdg7_FLc_0990, involved heat-shock protein 70-mediated nuclear importing mechanism. Overexpression of Cdg7_FLc_0990 in intestinal epithelial cells resulted in significant changes in expression levels of specific genes, with significant overlapping with alterations in gene expression profile detected in host cells after C. parvum infection. Our data demonstrate that C. parvum transcripts of low protein-coding potential are selectively delivered into epithelial cells during infection and may modulate gene transcription in infected host cells.
微小隐孢子虫是免疫功能低下个体的一种重要机会性寄生虫病原体，也是幼儿腹泻的常见病因。以往的研究已在微小隐孢子虫中鉴定出一组蛋白质编码潜力极低的RNA转录本。利用人肠道隐孢子虫病的体外模型，我们在此报告，在微小隐孢子虫感染期间，其中一些微小隐孢子虫RNA转录本被选择性地递送至宿主上皮细胞核内。几种此类寄生RNA（包括Cdg7_FLc_0990）的核递送涉及热休克蛋白70介导的核输入机制。Cdg7_FLc_0990在肠道上皮细胞中的过表达导致特定基因表达水平发生显著变化，与微小隐孢子虫感染后宿主细胞中检测到的基因表达谱改变有显著重叠。我们的数据表明，蛋白质编码潜力低的微小隐孢子虫转录本在感染期间被选择性地递送至上皮细胞，并可能调节受感染宿主细胞中的基因转录。
