A pathway analysis of poly(I:C)-induced global gene expression change in human peripheral blood mononuclear cells

Abstract

To gain global pathway perspective of ex vivo viral infection models using human peripheral blood mononuclear cells (PBMCs), we conducted expression analysis on PBMCs of healthy donors. RNA samples were collected at 3 and 24 h after PBMCs were challenged with the Toll-like receptor-3 (TLR3) agonist polyinosinic acid-polycytidylic acid [poly(I:C)] and analyzed by internally developed cDNA microarrays and TaqMan PCR. Our results demonstrate that poly(I:C) challenge can elicit certain gene expression changes, similar to acute viral infection. Hierarchical clustering revealed distinct immediate early, early-to-late, and late gene regulation patterns. The early responses were innate immune responses that involve TLR3, the NF-kappaB-dependent pathway, and the IFN-stimulated pathway, whereas the late responses were mostly cell-mediated immune response that involve activation of cell adhesion, cell mobility, and phagocytosis. Overall, our results expanded the utilities of this ex vivo model, which could be used to screen molecules that can modulate viral stress-induced inflammation, in particular those mediated via TLRs.

Mouse Embryonic Stem Cells Have Underdeveloped Antiviral Mechanisms That Can Be Exploited for the Development of mRNA-Mediated Gene Expression Strategy

“…However, it is interesting to note that the effect of base modifications cannot eliminate the immunogenicity since the effect is limited to a single transfection and the subsequent transfection of 10T1/2 cells with nGFPmRNA resulted in apparent antiviral responses. This can be explained by a well-documented phenomenon in antiviral responses; through a positive feedback loop, an initial weak stimulus (the first nGFP-mRNA transfection in our case) can upregulate the antiviral signaling pathways, thereby ''priming'' the cells to mount stronger antiviral responses to the subsequent stimulus (second nGFP-mRNA transfection) [50][51][52]. Therefore, immunogenicity intrinsically associated with mRNA (long ssRNA, sequence independent) can sensitize the host cells that have active antiviral mechanisms to repeated mRNA transfection.…”

Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice

“…1.6.1 Poly I:C Poly I:C is a synthetic analogue of double stranded RNA (dsRNA), considered to be a molecular pattern associated with viral infections [102,105,106]. This compound is able to activate the innate immune system via PRR signaling pathways [107].…”

“…and MDA-5 [102,[105][106][107]. In mammals, TLR3 expression has been detected in multiple cell types like ECs, fibroblasts, tumor cells, keratinocytes, DCs, macrophages and B cells [105,107].…”

Molecular cloning and expression analysis of a C-type lectin in the rock bream, Oplegnathus fasciatus

“…It is a potent inducer of type I interferon genes in fish that is known to induce some, but not all, of the stimulatory effects of viral dsRNA in higher vertebrates (Robertson, 2006;Huang et al, 2006).…”