1038/npp.2010.200; published online 15 December 2010″
“Type III interferons ([IFNs]IFN-lambda and interleukin-28 and -29 [IL-28/29]) are recently recognized cytokines with innate antiviral effects similar buy Combretastatin A4 to those of type I IFNs (IFN-alpha/beta). Like IFN-alpha/beta, IFN-lambda-expression can be induced by viruses, and it is believed that type I and III IFNs are regulated in the same manner. Hantaviruses are weak IFN-alpha/beta inducers and have surprisingly been
shown to activate IFN-alpha/beta-independent IFN-stimulated gene (ISG) expression. Here, we show that in Hantaan virus (HTNV)-infected human epithelial A549 cells, induction of IFN-lambda 1 preceded induction of MxA and IFN-beta by 12 and 24 h, respectively, Selleck AZD1480 and IFN-alpha was not induced at all. Furthermore, induction of
IFN-lambda 1 and MxA was observed in HTNV-infected African green monkey epithelial Vero E6 cells, a cell line that cannot produce type I IFNs, clearly showing that HTNV can induce IFN-lambda 1 and ISGs in the complete absence of IFN-alpha/beta. In HTNV-infected human fibroblast MRC-5 cells, which lack the IFN-lambda receptor, induction of MxA coincided in time with IFN-beta-induction. UV-inactivated HTNV did not induce any IFNs or MxA in any cell line, showing that activation of IFN-lambda 1 is dependent on replicating virus. Induction of both IFN-beta and IFN-lambda 1 in A549 cells after poly(I:C)-stimulation was strongly inhibited in HTNV-infected cells, suggesting that HTNV can inhibit signaling pathways used to simultaneously activate types I and III IFNs. In conclusion, we show that HTNV can cause type I IFN-independent IFN-lambda 1 induction and IFN-lambda 1-specific ISG induction.
Importantly, the results suggest the existence of specific signaling pathways that induce IFN-lambda 1 without simultaneous type I IFN induction during virus infection.”
“The dopamine receptor D2 (encoded by DRD2) is implicated in susceptibility to mental disorders and cocaine abuse, but mechanisms responsible for this relationship remain uncertain. DRD2 mRNA exists in two main splice isoforms with distinct functions: D2 long (D2L) and D2 short (D2S, lacking exon 6), expressed mainly postsynaptically and presynaptically, respectively. Two intronic single-nucleotide Immune system polymorphisms (SNPs rs2283265 (intron 5) and rs1076560 (intron 6)) in high linkage disequilibrium (LD) with each other have been reported to alter D2S/D2L splicing and several behavioral traits in human subjects, such as memory processing. To assess the role of DRD2 variants in cocaine abuse, we measured levels of D2S and D2L mRNA in human brain autopsy tissues (prefrontal cortex and putamen) obtained from cocaine abusers and controls, and genotyped a panel of DRD2 SNPs (119 abusers and 95 controls). Robust effects of rs2283265 and rs1076560 on reducing formation of D2S relative to D2L were confirmed.