Gopakumar Gayathri, Coppo Mauricio J C, Diaz-Méndez Andrés, Hartley Carol A, Devlin Joanne M
Asia-Pacific Centre for Animal Health, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Victoria, Australia.
Escuela de Medicina Veterinaria, Universidad Andrés Bello, Concepción, Biobío, Chile.
Microbiol Spectr. 2025 Feb 4;13(2):e0118324. doi: 10.1128/spectrum.01183-24. Epub 2025 Jan 13.
Previous studies have demonstrated the safety and efficacy of a live-attenuated glycoprotein G (gG) deletion mutant vaccine strain of ILTV (∆gG-ILTV). In the current study, transcriptional profiles of chicken tracheal organ cultures (TOCs), 24 h post inoculation with ∆gG-ILTV or the gG-expressing parent wild-type strain, CSW-1 ILTV were explored and compared with the mock-infected TOCs using RNA-seq analysis. Transcriptomes of the vaccine and wild-type ILTV were also compared with each other. Although no viral genes (except for gG) were differentially regulated between the two ILTV-infected TOCs, pair-wise comparison of the transcriptomes of the ∆gG-ILTV or the CSW-1 ILTV-infected TOCs (each compared with mock-infected TOCs) identified the similarities and differences in host gene transcription between them. Several immune checkpoint inhibitors with likely roles in ILTV-mediated immune augmentation, and gene ontologies indicating cytokine response, and cytokine signaling were upregulated in both TOCs. Additionally, several other biological processes, molecular functions, and cellular components were enriched uniquely in the ∆gG-ILTV-infected TOCs, including those that indicated modifications to tracheal extracellular matrix (ECM) structural components, which may have a role in immune modulation . This study has revealed that the modifications of transcription of host genes during the early stages of ILTV infection are not limited to changes in cytokine or chemokine gene transcription, but several other immune-related genes and ECM components. Moreover, their differential regulation in the system appears to be influenced by gG expression, potentially affecting the outcome of ILTV infection .IMPORTANCEInfectious laryngotracheitis virus (ILTV) remains a serious threat to poultry industries worldwide, causing significant economic losses. The glycoprotein G (gG) of ILTV is a virulence factor and a chemokine-binding protein with immunoregulatory functions. The influence of gG on the transcription of select host chemokine and cytokine genes has been demonstrated previously. This study extends our understanding of the early and localized host-ILTV interactions using genome-wide transcriptome analysis of ILTV-infected chicken tracheal organ cultures, and the role of gG during the process. Differential regulation of genes encoding immune checkpoint inhibitors observed in this study may have a role in ILTV-induced inhibition of type I interferon response, or negative regulation of T cell responses, bringing clarity to these ILTV immune-evasion mechanisms. Furthermore, differential regulation of genes encoding certain structural components and receptors with roles in cell migration, in the absence of gG, is consistent with the immunomodulatory role of ILTV gG.
先前的研究已证明传染性喉气管炎病毒（ILTV）的减毒活糖蛋白G（gG）缺失突变疫苗株（∆gG-ILTV）的安全性和有效性。在本研究中，利用RNA测序分析探索并比较了接种∆gG-ILTV或表达gG的亲本野生型毒株CSW-1 ILTV 24小时后鸡气管器官培养物（TOC）的转录谱，并与模拟感染的TOC进行了比较。还对疫苗和野生型ILTV的转录组进行了相互比较。尽管在两种ILTV感染的TOC之间，除gG外没有病毒基因受到差异调节，但对∆gG-ILTV或CSW-1 ILTV感染的TOC的转录组进行成对比较（分别与模拟感染的TOC比较），确定了它们之间宿主基因转录的异同。在两种TOC中，几种可能在ILTV介导的免疫增强中起作用的免疫检查点抑制剂以及表明细胞因子反应和细胞因子信号传导的基因本体均上调。此外，在∆gG-ILTV感染的TOC中，几种其他生物学过程、分子功能和细胞成分被独特富集，包括那些表明气管细胞外基质（ECM）结构成分发生改变的过程，这可能在免疫调节中起作用。本研究表明，ILTV感染早期宿主基因转录的改变不仅限于细胞因子或趋化因子基因转录的变化，还包括其他一些免疫相关基因和ECM成分。此外，它们在该系统中的差异调节似乎受gG表达的影响，可能影响ILTV感染的结果。
重要性
传染性喉气管炎病毒（ILTV）仍然是全球家禽业的严重威胁，造成重大经济损失。ILTV的糖蛋白G（gG）是一种毒力因子，也是一种具有免疫调节功能的趋化因子结合蛋白。先前已证明gG对选定宿主趋化因子和细胞因子基因转录的影响。本研究通过对ILTV感染的鸡气管器官培养物进行全基因组转录组分析，扩展了我们对早期和局部宿主-ILTV相互作用以及gG在此过程中的作用的理解。本研究中观察到的编码免疫检查点抑制剂的基因的差异调节可能在ILTV诱导的I型干扰素反应抑制或T细胞反应的负调节中起作用，从而阐明了这些ILTV免疫逃逸机制。此外，在没有gG的情况下，编码在细胞迁移中起作用的某些结构成分和受体的基因的差异调节与ILTV gG的免疫调节作用一致。
