Drechsler Yvonne, Vasconcelos Elton J R, Griggs Lisa M, Diniz Pedro P P V
College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA, United States.
Leeds Omics, University of Leeds, Leeds, United Kingdom.
Front Genet. 2020 Dec 3;11:584744. doi: 10.3389/fgene.2020.584744. eCollection 2020.
Coronaviruses are highly infectious and common in many species, including in humans, and agricultural and domestic animals. Host responses play an important role in viral entry, replication, assembly, and pathogenesis, although much is still to be understood, particularly host-virus interactions. Feline coronavirus is highly contagious, and ubiquitous in virtually all cat populations. Host-pathogen interactions have not been studied extensively due to the complex pathogenesis and development of clinical disease. Few studies have investigated cellular host responses to feline coronavirus infection, particularly at early time points. Transcriptome studies based on next-generation sequencing have the potential to elucidate the early responses of cells after viral infection and, consequently, give further insight into the pathogenesis of viruses. The current study aims to characterize and compare the viral- and immune-related differentially expressed genes in response to the coronavirus FIPV across different time points in a cell line which is permissive for productive replication versus primary cells implicated in pathogenesis. When comparing host responses in Crandell-Rees Feline Kidney (CRFK) cells to primary macrophages, many differences were observed with regards to expressed genes and their enrichments for both KEGG pathways and GO terms. CRFK cells which are permissive for productive replication of feline infectious peritonitis virus, showed induction of a large network of immunological and virally induced pathways. In contrast, Macrophages did not show similar host responses, with stronger pathway enrichment in downregulated transcripts. This study provides insights to better understand gene transcription in immune cells compared to epithelial cells discerning pathways relevant to pathogenesis in the early stages of infection.
冠状病毒具有高度传染性,在包括人类、家畜和家禽在内的许多物种中都很常见。宿主反应在病毒的进入、复制、组装和发病机制中起着重要作用,尽管仍有许多有待了解,尤其是宿主与病毒的相互作用。猫冠状病毒具有高度传染性,几乎在所有猫群体中都普遍存在。由于临床疾病发病机制复杂,宿主与病原体的相互作用尚未得到广泛研究。很少有研究调查细胞对猫冠状病毒感染的宿主反应,尤其是在早期阶段。基于下一代测序的转录组研究有潜力阐明病毒感染后细胞的早期反应,从而进一步深入了解病毒的发病机制。本研究旨在表征和比较在一个允许有效复制的细胞系与参与发病机制的原代细胞中,针对冠状病毒猫传染性腹膜炎病毒(FIPV)在不同时间点的病毒和免疫相关差异表达基因。当比较克兰德尔-里斯猫肾(CRFK)细胞与原代巨噬细胞中的宿主反应时,在表达基因及其对KEGG通路和GO术语的富集方面观察到许多差异。对猫传染性腹膜炎病毒有效复制具有允许性的CRFK细胞,显示出大量免疫和病毒诱导通路网络的诱导。相比之下,巨噬细胞没有显示出类似的宿主反应,在下调转录本中有更强的通路富集。这项研究为更好地理解免疫细胞与上皮细胞相比的基因转录提供了见解,识别出感染早期与发病机制相关的通路。