The interplay between viral-derived miRNAs and host immunity during infection

MicroRNAs are short non-coding RNAs that play a crucial role in the regulation of gene expression during cellular processes. The host-encoded miRNAs are known to modulate the antiviral defense during viral infection. In the last decade, multiple DNA and RNA viruses have been shown to produce miRNAs known as viral miRNAs (v-miRNAs) so as to evade the host immune response. In this review, we highlight the origin and biogenesis of viral miRNAs during the viral lifecycle. We also explore the role of viral miRNAs in immune evasion and hence in maintaining chronic infection and disease. Finally, we offer insights into the underexplored role of viral miRNAs as potential targets for developing therapeutics for treating complex viral diseases

Enteric viral co-infections: Pathogenesis and perspective

Enteric viral co-infections, infections involving more than one virus, have been reported for a diverse group of etiological agents, including rotavirus, norovirus, astrovirus, adenovirus, and enteroviruses. These pathogens are causative agents for acute gastroenteritis and diarrheal disease in immunocompetent and immunocompromised individuals of all ages globally. Despite virus-virus co-infection events in the intestine being increasingly detected, little is known about their impact on disease outcomes or human health. Here, we review what is currently known about the clinical prevalence of virus-virus co-infections and how co-infections may influence vaccine responses. While experimental investigations into enteric virus co-infections have been limited, we highlight in vivo and in vitro models with exciting potential to investigate viral co-infections. Many features of virus-virus co-infection mechanisms in the intestine remain unclear, and further research will be critical

A human STAT1 gain-of-function mutation impairs CD8 + T cell responses against gammaherpesvirus 68

Autosomal dominant STAT1 mutations in humans have been associated with chronic mucocutaneous candidiasis (CMC), as well as with increased susceptibility to herpesvirus infections. Prior studies have focused on mucosal and Th17-mediated immunity agains

Homeostatic interferon-lambda response to bacterial microbiota stimulates preemptive antiviral defense within discrete pockets of intestinal epithelium

Interferon-lambda (IFN-λ) protects intestinal epithelial cells (IECs) from enteric viruses by inducing expression of antiviral IFN-stimulated genes (ISGs). Here, we find that bacterial microbiota stimulate a homeostatic ISG signature in the intestine of specific pathogen-free mice. This homeostatic ISG expression is restricted to IECs, depends on IEC-intrinsic expression of IFN-λ receptor

Intestinal antiviral signaling is controlled by autophagy gene Epg5 independent of the microbiota

Mutations in the macroautophagy/autophagy gen

Distinct Effects of Type I and III Interferons on Enteric Viruses

Interferons (IFNs) are key host cytokines in the innate immune response to viral infection, and recent work has identified unique roles for IFN subtypes in regulating different aspects of infection. Currently emerging is a common theme that type III IFNs are critical in localized control of infection at mucosal barrier sites, while type I IFNs are important for broad systemic control of infections. The intestine is a particular site of interest for exploring these effects, as in addition to being the port of entry for a multitude of pathogens, it is a complex tissue with a variety of cell types as well as the presence of the intestinal microbiota. Here we focus on the roles of type I and III IFNs in control of enteric viruses, discussing what is known about signaling downstream from these cytokines, including induction of specific IFN-stimulated genes. We review viral strategies to evade IFN responses, effects of IFNs on the intestine, interactions between IFNs and the microbiota, and briefly discuss the role of IFNs in controlling viral infections at other barrier sites. Enhanced understanding of the coordinate roles of IFNs in control of viral infections may facilitate development of antiviral therapeutic strategies; here we highlight potential avenues for future exploration

Predictors of 1-month and 3-months Hospital Readmissions in Decompensated Cirrhosis: A Prospective Study in a Large Asian Cohort

Introduction and aim: Considered as a healthcare quality indicator, hospital readmissions in decompensated cirrhosis predispose the patients and the society to physical, social and economic distresses. Few studies involving North American cohorts have identified different predictors. The aim of this study was to determine and validate the predictors of 1-month and 3-months readmission in an Asian cohort. Material and methods.: We prospectively studied 281 hospitalised patients with decompensated cirrhosis at a large tertiary care public hospital in India between August 2014 and August 2016 and followed them for 3 months. Data regarding demographic, laboratory and disease related risk factors were compiled. We used multivariate logistic regression to determine predictors of readmission at 1-month and 3-months and receiver operating curves (ROC) for significant predictors to obtain the best cut-offs. Results: 1-month and 3-months readmission rates in our study were 27.8% and 42.3%, respectively. Model for End stage Liver Disease (MELD) score at discharge (OR:1.24, p 14 at discharge and serum sodium < 133 mEq/L best predicted readmissions; MELD score being a better predictor than serum sodium (p - 0.0001). Conclusions: High rates of early and late readmissions were found in our study. Further, this study validated readmission predictors in Asian patients. Structured interventions targeting this risk factors may diminish readmissions in decompensated cirrhosis