Dataset Information

ISG15: It's Complicated.

ABSTRACT: Interferon-stimulated gene product 15 (ISG15) is a key component of host responses to microbial infection. Despite having been known for four decades, grasping the functions and features of ISG15 has been a slow and elusive process. Substantial work over the past two decades has greatly enhanced this understanding, revealing the complex and variable nature of this protein. This has unveiled multiple mechanisms of action that are only now beginning to be understood. In addition, it has uncovered diversity not only between how ISG15 affects different pathogens but also between the function and structure of ISG15 itself between different host species. Here we review the complexity of ISG15 within the context of viral infection, focusing primarily on its antiviral function and the mechanisms viruses employ to thwart its effects. We highlight what is known regarding the impact of ISG15 sequence and structural diversity on these interactions and discuss the aspects presenting the next frontier toward elucidating a more complete picture of ISG15 function.

SUBMITTER: Dzimianski JV

PROVIDER: S-EPMC6746611 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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ISG15: It's Complicated.

Dzimianski John V JV Scholte Florine E M FEM Bergeron Éric É Pegan Scott D SD

Journal of molecular biology 20190316 21

Interferon-stimulated gene product 15 (ISG15) is a key component of host responses to microbial infection. Despite having been known for four decades, grasping the functions and features of ISG15 has been a slow and elusive process. Substantial work over the past two decades has greatly enhanced this understanding, revealing the complex and variable nature of this protein. This has unveiled multiple mechanisms of action that are only now beginning to be understood. In addition, it has uncovered ...[more]

PMID: 30890331

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Project description:Each microbe has the ability to produce a wide variety of sugar structures that includes some combination of glycolipids, glycoproteins, exopolysaccharides and oligosaccharides. For example, bacteria may synthesize lipooligosaccharides or lipopolysaccharides, teichoic and lipoteichoic acids, N- and O-linked glycoproteins, capsular polysaccharides, exopolysaccharides, poly-N-acetylglycosamine polymers, peptidoglycans, osmoregulated periplasmic glucans, trehalose or glycogen, just to name a few of the more broadly distributed carbohydrates that have been studied. The composition of many of these glycans are typically dissimilar from those described in eukaryotes, both in the seemingly endless repertoire of sugars that microbes are capable of synthesizing, and in the unique modifications that are attached to the carbohydrate residues. Furthermore, strain-to-strain differences in the carbohydrate building blocks used to create these glycoconjugates are the norm, and many strains possess additional mechanisms for turning on and off transferases that add specific monosaccharides and/or modifications, exponentially contributing to the structural heterogeneity observed by a single isolate, and preventing any structural generalization at the species level. In the past, a greater proportion of research effort was directed toward characterizing human pathogens rather than commensals or environmental isolates, and historically, the focus was on microbes that were simple to grow in large quantities and straightforward to genetically manipulate. These studies have revealed the complexity that exists among individual strains and have formed a foundation to better understand how other microbes, hosts and environments further transform the glycan composition of a single isolate. These studies also motivate researchers to further explore microbial glycan diversity, particularly as more sensitive analytical instruments and methods are developed to examine microbial populations in situ rather than in large scale from an enriched nutrient flask. This review emphasizes many of these points using the common foodborne pathogen Campylobacter jejuni as the model microbe.

Project description:ObjectivesInternationally, public health strategies encourage health care professionals to deliver opportunistic behaviour change interventions. The present study: (1) examines the barriers and enablers to delivering interventions during routine consultations, and (2) provides recommendations for the design of interventions to increase delivery of opportunistic behaviour change interventions.DesignQualitative interview study.MethodsTwenty-eight semi-structured interviews were conducted with patient-facing health care professionals. The Behaviour Change Wheel informed a framework analysis in which findings were mapped onto the Theoretical Domains Framework (TDF). Intervention functions and behaviour change techniques (BCTs) targeting each TDF domain were identified.ResultsHealth care professionals understood the importance of opportunistic behaviour change interventions (beliefs about consequences), but were sceptical about their capabilities to facilitate behaviour change with patients (beliefs about capabilities). Some clinicians were unwilling to discuss behaviours perceived as unrelated to the patient's visit (social/professional role and identity). Discipline-specific tasks were prioritized, and delivering interventions was perceived as psychologically burdensome. One-to-one contact was favoured over busy hospital settings (environmental context and resources). Seven intervention functions (training, restriction, environmental restructuring, enablement, education, persuasion, and modelling) and eight BCT groupings (antecedents, associations, comparison of outcomes, covert learning, feedback and monitoring, natural consequences, reward and threat, and self-belief) were identified.ConclusionsAcross disciplines, health care professionals see the value of opportunistic behaviour change interventions. Barriers related to workload, the clinical environment, competence, and perceptions of the health care professional role must be addressed, using appropriate intervention functions and BCTs, in order to support health care professionals to increase the delivery of interventions in routine practice. Statement of contribution What is already known on this subject? Brief, opportunistic interventions can be a cost effective way of addressing population health problems. Public health policies compel health care professionals to deliver behaviour change interventions opportunistically. Health care professionals do not always deliver interventions opportunistically during routine medical consultations; however the barriers and enablers are currently unclear. What does this study add? This is the first study to examine cross-disciplinary barriers and enablers to delivering opportunistic behaviour change interventions. Across diverse professional groups, working in different medical professions, participants saw the value of delivering opportunistic behaviour change interventions. Targeting key theoretical domains that are shared across professional groups may be useful for increasing the delivery of opportunistic behaviour change interventions.

Dataset Information

ISG15: It's Complicated.

Publications

ISG15: It's Complicated.

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