The Gene Expression Profile of Peripheral Blood Mononuclear Cells from EV71-Infected Rhesus Infants and the Significance in Viral Pathogenesis

Abstract

Enterovirus 71 (EV71) is the major pathogen responsible for fatal hand, foot and mouth disease (HFMD). Our previous work reported on an EV71-infected rhesus monkey infant model that presented with histo-pathologic changes of the central nervous system (CNS) and lungs. This study is focused on the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs) from EV71-infected rhesus monkey infants. The expression of more than 500 functional genes associated with multiple pathways was modulated. The expression of genes associated with immune inflammatory responses was up-regulated during the period from days 4 to 10 post-infection. The expression of two genes (TAC1 and IL17A), which play major roles in inflammatory reactions, was remarkably up-regulated during the infection period. Furthermore, a higher expression level of the TAC1 gene was identified in the CNS compared to the lungs, but a high expression level of the IL-17A gene was observed in the lungs and not in the CNS. The results of this study suggest at least two facts about EV71 infection, which are that: the TAC1 gene that encodes substance P and neurokinin-A is present in both PBMCs and the hypothalamus; and the up-regulation of IL-17A is sustained in the peripheral blood.

Global Gene Expression Analysis of the Brainstem in EV71- and CVA16-Infected Gerbils

“…Jin identified 1825 genes that were upregulated and 129 genes that were downregulated in CVA16-infected HEK293T cells compared with the CVA16-non-infected samples [16]. Zhang found more than 1000 genes that were up-or downregulated in the peripheral blood mononuclear cells of EV71-infected rhesus monkey infants compared with the EV71-non-infected groups [17]. Among all DEGs, the number of upregulated genes was 3 times greater than that of downregulated genes in both EV71-and CVA16-infected gerbils.…”

Association of Interleukin-17F gene polymorphisms with susceptibility to severe enterovirus 71 infection in Chinese children

“…Huppet et al also reported that IL-17 induced BBB disruption through the formation of reactive oxygen species (ROS) by NAD(P)H oxidase and xanthine oxidase, which are subsequently responsible for the disruption and downregulation of tight junction molecules and the activation of IL-17F levels in T/T and C/T genotypes were significantly higher than with C/C genotypes in severe cases (***p < 0.001, *p < 0.05), but there were no differences between different genotypes in mild cases the endothelial contractile machinery [40]. Furthermore, in the EV71-infected rhesus monkey infant model, the upregulation of IL-17 was sustained in the peripheral blood [15]. ROR γt has been proven to be the key transcription factor for the differentiation of Th17 cells and the release of IL-17 [41].…”

“…Based on clinical manifestations and animal experiments [12][13][14][15], one hypothesis is that the inflammatory response, characterized by a cytokine storm, is induced by EV71 infection and subsequently leads to pathological changes in the central nervous system (CNS), resulting in further disruption of CNS stability. Anti-virus infections are often dominated by a Th1 response.…”

microRNA expression profiling in human diploid cells infected with enterovirus 71 or coxsackievirus A16

“…To explore the potential rationale for the diversity in the immune response in humans infected by EV71 and CA16, our previous works analyzed the gene expression profiles in peripheral blood mononuclear cells (PBMCs) of rhesus macaques infected with these two viruses. The results showed that EV71 and CA16 infections could distinctively induce a wide variety of host genes, specifically, immune-associated genes such as interleukin (IL)-4 and IL-17 [19,20].…”