Division of Biological Sciences, University of California, San Diego, La Jolla, California, CA, USA.
Department of Cell Biology, New York University School of Medicine, New York, NY, USA.
Nat Commun. 2022 Jan 10;13(1):17. doi: 10.1038/s41467-021-27621-w.
Defense against intracellular infection has been extensively studied in vertebrate hosts, but less is known about invertebrate hosts; specifically, the transcription factors that induce defense against intracellular intestinal infection in the model nematode Caenorhabditis elegans remain understudied. Two different types of intracellular pathogens that naturally infect the C. elegans intestine are the Orsay virus, which is an RNA virus, and microsporidia, which comprise a phylum of fungal pathogens. Despite their molecular differences, these pathogens induce a common host transcriptional response called the intracellular pathogen response (IPR). Here we show that zip-1 is an IPR regulator that functions downstream of all known IPR-activating and regulatory pathways. zip-1 encodes a putative bZIP transcription factor, and we show that zip-1 controls induction of a subset of genes upon IPR activation. ZIP-1 protein is expressed in the nuclei of intestinal cells, and is at least partially required in the intestine to upregulate IPR gene expression. Importantly, zip-1 promotes resistance to infection by the Orsay virus and by microsporidia in intestinal cells. Altogether, our results indicate that zip-1 represents a central hub for triggers of the IPR, and that this transcription factor has a protective function against intracellular pathogen infection in C. elegans.
脊椎动物宿主的细胞内感染防御已得到广泛研究，但对无脊椎动物宿主的了解较少；具体来说，模型线虫秀丽隐杆线虫中诱导细胞内肠道感染防御的转录因子仍研究不足。两种不同类型的天然感染秀丽隐杆线虫肠道的细胞内病原体是 Orsay 病毒，它是一种 RNA 病毒，和微孢子虫，它是真菌病原体的一个门。尽管它们的分子不同，但这些病原体诱导一种称为细胞内病原体反应（IPR）的常见宿主转录反应。在这里，我们表明 zip-1 是一种 IPR 调节剂，它位于所有已知的 IPR 激活和调节途径的下游。zip-1 编码一个假定的 bZIP 转录因子，我们表明 zip-1 控制 IPR 激活时的一组基因的诱导。ZIP-1 蛋白在肠细胞的核内表达，并且至少部分需要在肠道中上调 IPR 基因表达。重要的是，zip-1 促进了 Orsay 病毒和微孢子虫在肠细胞中的感染抵抗。总之，我们的结果表明 zip-1 代表了 IPR 触发因素的中央枢纽，并且该转录因子在秀丽隐杆线虫的细胞内病原体感染中具有保护功能。
