Interferon-(IFN-) is an antiviral cytokine that signals through a distinct receptor complex, composed of the IFN-R1and interleukin-10R2 (IL-10R2) receptor chains. We have determined the crystal structure of human IFN-3 and characterized the interaction with its receptor complex through structurebased site-directed mutagenesis. The ability of IFN-3 mutants to signal was determined by measuring the antiviral activity and induced STAT2 phosphorylation. In conclusion, our data show that, although IFN-is functionally an interferon, it is clearly structurally related to members of the IL-10 family. In particular, we found an interesting similarity between IFN-and IL-22, and we suggest that IFN-and IL-22 possess parallel functions, protecting epithelial tissue against viral and bacterial infections, respectively.In 2003, a novel family of cytokines was discovered simultaneously by two independent research teams (1, 2). Initially, the two research teams named these novel cytokines either interferon-(IFN-) 2 1, 2, and 3 or interleukin-29 (IL-29), -28A, or -28B. Throughout this report we will use the IFN-designation or type III IFN, when referring to all tree subtypes as a group. Like type I IFN, type III IFN induces antiviral activity both in vitro (3, 4) and in vivo (5). Thus the two types of IFN seem to have similar biological effects at a cellular level. IFN-uses a distinct receptor complex consisting of a unique subunit, named IFN-R1, as well as the IL-10R2 subunit. The similar biological effects caused by type I and III IFN can be explained by activation of a highly overlapping set of transcription factors. In particular, both types of IFN lead to phosphorylation of signal transducers and activators of transcription (STAT) 1, 2, and 3, followed by assembly of the interferon-stimulated gene factor 3 transcription factor and thus target the same population of genes for induction (6 -8).The expression of type III IFN appears to be induced by the same stimuli and depend upon the same signaling pathways as type I IFN. For example, type III IFN has been shown to be induced by a variety of viruses such as influenza A virus, herpes viruses, and Sendai virus as well as lipopolysaccharides or double-stranded RNA (9 -11). However, the contribution of different cell populations to the production of IFN-is not yet clear. An important difference between the type I and III IFN systems is the expression pattern of their receptors. Whereas most cell types express the type I IFN receptor complex and the IL-10R2 component of the IFN-receptor, the expression of the IFN-R1 receptor subunit is highly restricted (12, 13). The exact expression pattern of the IFN-R1 is not yet fully established, but it is clear that cells of epithelial origin express IFN-R1 (13). Because type III IFN cannot signal without both receptor subunits, the response to type III IFN is restricted as well. Recent work, using IFN-R1 knock-out mice, demonstrated that IFN-is effective against influenza virus, if the virus is administrated through the intranasal route, b...

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Type III interferon (IFN) or IFN-lambda is a recently discovered family of IFNs that signal through the same downstream transcription factors as type I IFN but use a separate receptor complex composed of the IL-10R2 and the unique IFN-lambdaR1 receptor chains. We have established a simple and efficient expression system to produce highly pure and active IFN-lambda of the three human IFN-lambda isoforms (IFN-lambda1, -lambda2 and -lambda3) and used this to compare the biological activity of the different IFN-lambda subtypes. Surprisingly, we found IFN-lambda3 to possess the highest specific activity of the human IFN-lambda subtypes, exhibiting a twofold higher activity than IFN-lambda1 and a 16-fold higher activity than IFN-lambda2. Furthermore, in comparison with the commercially available preparations of IFN-lambda1 and -lambda2, we found our IFN-lambda preparation to be superior in activity.

Objectives: Next-generation sequencing (NGS) for the determination of rare blood group genotypes was tested in 72 individuals from different ethnicities.Background: Traditional serological-based antigen detection methods, as well as genotyping based on specific single nucleotide polymorphisms (SNPs) or single nucleotide variants (SNVs), are limited to detecting only a limited number of known antigens or alleles. NGS methods do not have this limitation.Methods: NGS using Ion torrent Personal Genome Machine (PGM) was performed with a customised Ampliseq panel targeting 15 different blood group systems on 72 blood donors of various ethnicities (Caucasian, Hispanic, Asian, Middle Eastern and Black).Results: Blood group genotypes for 70 of 72 samples could be obtained for 15 blood group systems in one step using the NGS assay and, for common SNPs, are consistent with previously determined genotypes using commercial SNP assays. However, particularly for the Kidd, Duffy and Lutheran blood group systems, several SNVs were detected by the NGS assay that revealed additional coding information compared to other methods. Furthermore, the NGS assay allowed for the detection of genotypes related to VEL, Knops, Gerbich, Globoside, P1PK and Landsteiner-Wiener blood group systems. Conclusions:The NGS assay enables a comprehensive genotype analysis of many blood group systems and is capable of detecting common and rare alleles, including alleles not currently detected by commercial assays.