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This study provides an accurate awareness of the present situation of health research in Irish hospitals both public and private. We aimed to analyze factors that may influence it and provide recommendations for active steps to improve the current situation of Irish health research based on our findings. We performed a bibliometric analysis to assess qualitatively and quantitatively the publications from Ireland over a period between 2007 and 2018. We also investigated the associated variables with the quality of research. Furthermore, we conducted a Joinpoint analysis to see the trends in Irish research over these years. From 12,828 included peer-reviewed articles, the average citation count per article was 19.98. Furthermore, we showed that a higher impact factor (IF) and institutions number, present per article, were significantly associated with more citations. Also, the publication count and the mean IF showed an increase over the years according to the Joinpoint analysis. Moreover, the oncology research had the highest output, followed by pediatrics, then neurology while the specialties with least publications were ear, nose, and throat (ENT), urology, plastic surgery, and dentistry. Additionally, cardiovascular, obstetrics and gynecology, oncology, pediatrics, pulmonology, dermatology, ophthalmology, dentistry, and radiology research showed an increased publication count trend in recent years. While anesthesiology, ENT, general surgery, gastroenterology and hepatology, infection and tropical medicine, nephrology, neurology, orthopedics, plastic surgery, and urology showed a decrease in the publications trend. Our findings may serve as a useful approach to benchmark scientific output from hospitals and guide the future allocation of research spending.

Hematopoietic stem cell (HSC) transplanted humanized mice are a valuable small animal model for preclinical testing of HSC-based gene therapies, since the engraftment and subsequent differentiation of the cells in the mice allows a rigorous assessment of whether the genetic manipulation in any way impacts HSC function. In addition, since the HSC give rise to human CD4+ T cells, the mice can support an HIV-1 infection. This means that the mice are particularly suited to the evaluation of anti-HIV gene therapies, where the actual target human cell and gene therapy reagents can be evaluated in a system that supports infection by the authentic human virus. In this chapter we review the role played by humanized mouse models in the preclinical development of a promising anti-HIV approach based on disruption of the human CCR5 gene in human HSC, using zinc finger nuclease editing.

Detection of viral nucleic acid within infected cells is essential to an effective anti-viral response. The retinoic acid-inducible gene-I-like receptors (RLR) form part of the virus detection repertoire and are critically important in sensing viral RNA in the cytoplasm. Efforts continue to define the signalling components downstream of RLR that are required to induce type I IFN (IFN-α and promoter stimulator-1) after viral infection. One surprising finding was that the Asp-Glu-Ala-Asp box helicase DEAD/H Box 3 (DDX3), known for some time to have a number of roles in cellular RNA regulation in the nucleus, has a role in the RLR cytoplasmic signalling pathway involved in promoter stimulator-1 induction. In this issue of the European Journal of Immunology, an article reports an additional distinct positive role for DDX3 in the RLR RNA sensing pathway. This further emphasises the importance of DDX3 in anti-viral immunity, and is consistent with the idea that viruses target DDX3 for immune evasion.

A systems approach provides a global perspective of the different strategies that viruses use to modulate the cellular innate immune response; this may be useful in the design of future viral intervention strategies. Andreas Pichlmair et al. take a systems approach to obtain a global perspective of the different strategies that viruses use to modulate the cellular innate immune response. The results demonstrate that viruses have evolved to exploit a variety of cellular mechanisms, and suggest that the host cell relies on homeostatic regulation across these diverse cellular processes to defend itself against pathogen interference. A central goal of this work is to identify common targets and general network properties in the host antiviral defence system that may be useful in the design of future viral-intervention strategies. Viruses must enter host cells to replicate, assemble and propagate. Because of the restricted size of their genomes, viruses have had to evolve efficient ways of exploiting host cell processes to promote their own life cycles and also to escape host immune defence mechanisms1,2. Many viral open reading frames (viORFs) with immune-modulating functions essential for productive viral growth have been identified across a range of viral classes3,4. However, there has been no comprehensive study to identify the host factors with which these viORFs interact for a global perspective of viral perturbation strategies5,6,7,8,9,10,11. Here we show that different viral perturbation patterns of the host molecular defence network can be deduced from a mass-spectrometry-based host-factor survey in a defined human cellular system by using 70 innate immune-modulating viORFs from 30 viral species. The 579 host proteins targeted by the viORFs mapped to an unexpectedly large number of signalling pathways and cellular processes, suggesting yet unknown mechanisms of antiviral immunity. We further experimentally verified the targets heterogeneous nuclear ribonucleoprotein U, phosphatidylinositol-3-OH kinase, the WNK (with-no-lysine) kinase family and USP19 (ubiquitin-specific peptidase 19) as vulnerable nodes in the host cellular defence system. Evaluation of the impact of viral immune modulators on the host molecular network revealed perturbation strategies used by individual viruses and by viral classes. Our data are also valuable for the design of broad and specific antiviral therapies.

Detection of viral nucleic acid within infected cells is essential to an effective anti-viral response. The retinoic acid-inducible gene-I-like receptors (RLR) form part of the virus detection repertoire and are critically important in sensing viral RNA in the cytoplasm. Efforts continue to define the signalling components downstream of RLR that are required to induce type I IFN (IFN-alpha and promoter stimulator-1) after viral infection. One surprising finding was that the Asp-Glu-Ala-Asp box helicase DEAD/H Box 3 (DDX3), known for some time to have a number of roles in cellular RNA regulation in the nucleus, has a role in the RLR cytoplasmic signalling pathway involved in promoter stimulator-1 induction. In this issue of the European Journal of Immunology, an article reports an additional distinct positive role for DDX3 in the RLR RNA sensing pathway. This further emphasises the importance of DDX3 in anti-viral immunity, and is consistent with the idea that viruses target DDX3 for immune evasion.

In recent years an explosion of information on the various strategies viruses employ to penetrate and hijack the host cell has led to an increased understanding of both viruses themselves and the host immune response. Despite their simplicity viruses have evolved a number of strategies to not only evade the host immune response but also modulate immune signalling to favour their replication and survival within the cell. The innate immune response provides the host with an early reaction against viruses. This response relies heavily upon the recognition of pathogen-associated molecular patterns (PAMPs) by a number of host pattern recognition receptors (PRRs), leading to activation of innate signalling pathways and altered gene expression. In this chapter we outline the signalling pathways that respond to viral infection and the various methods that viruses utilize to evade detection and modulate the innate immune response to favour their survival.

In recent years an explosion of information on the various strategies viruses employ to penetrate and hijack the host cell has led to an increased understanding of both viruses themselves and the host immune response. Despite their simplicity viruses have evolved a number of strategies to not only evade the host immune response but also modulate immune signalling to favour their replication and survival within the cell. The innate immune response provides the host with an early reaction against viruses. This response relies heavily upon the recognition of pathogen-associated molecular patterns (PAMPs) by a number of host pattern recognition receptors (PRRs), leading to activation of innate signalling pathways and altered gene expression. In this chapter we outline the signalling pathways that respond to viral infection and the various methods that viruses utilize to evade detection and modulate the innate immune response to favour their survival.