Crosstalk between Nucleotide Synthesis Pathways with Cellular Immunity in Constraining Hepatitis E Virus Replication

Wang, Y.; Wang, W.; Xu, Liangheng; Zhou, Xiaojun; Felczak, Krzysztof; Laan, Ljw van der; Pankiewicz, Krzysztof W.; Sprengers, Dave; Metselaar, HJ; Peppelenbosch, Maikel P.; Pan, Qiaoling

doi:10.1016/s0168-8278(16)00937-5

Cited by 1 publication

(1 citation statement)

References 41 publications

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“…It is of note that purines may participate in the cell-danger response (Naviaux 2014), in crosstalk between nucleotide synthesis and host cell innate immune responses (Wang et al . 2017; Wang et al . 2016), and in autocrine signaling (Xia et al .…”

Section: Discussionmentioning

confidence: 99%

Expression of the purine biosynthetic enzyme phosphoribosyl formylglycinamidine synthase in neurons

Mangold

Yao

et al. 2018

Journal of Neurochemistry

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Purines are metabolic building blocks essential for all living organisms on earth. De novo purine biosynthesis occurs in the brain and appears to play important roles in neural development. Phosphoribosyl formylglycinamidine synthase (FGAMS, also known as PFAS or FGARAT), a core enzyme involved in the de novo synthesis of purines, may play alternative roles in viral pathogenesis. To date, no thorough investigation of the endogenous expression and localization of de novo purine biosynthetic enzymes has been conducted in human neurons or in virally infected cells. In this study, we characterized expression of FGAMS using multiple neuronal models. In differentiated human SH-SY5Y neuroblastoma cells, primary rat hippocampal neurons, and in whole-mouse brain sections, FGAMS immunoreactivity was distributed within the neuronal cytoplasm. FGAMS immunolabeling in vitro demonstrated extensive distribution throughout neuronal processes. To investigate potential changes in FGAMS expression and localization following viral infection, we infected cells with the human pathogen herpes simplex virus 1. In infected fibroblasts, FGAMS immunolabeling shifted from a diffuse cytoplasmic location to a mainly perinuclear localization by 12 h post-infection. In contrast, in infected neurons, FGAMS localization showed no discernable changes in the localization of FGAMS immunoreactivity. There were no changes in total FGAMS protein levels in either cell type. Together, these data provide insight into potential purine biosynthetic mechanisms utilized within neurons during homeostasis as well as viral infection. Cover Image for this Issue: doi: 10.1111/jnc.14169.

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