Using Diverse Model Systems to Define Intestinal Epithelial Defenses to Enteric Viral Infections

Abstract

The intestine is an essential physical and immunological barrier comprised of a monolayer of diverse and specialized epithelial cells that perform functions ranging from nutrient absorption to pathogen sensing and intestinal homeostasis. The intestinal barrier prevents translocation of intestinal microbes into internal compartments. The microbiota is comprised of a complex community largely populated by diverse bacterial species that provide metabolites, nutrients, and immune stimuli that promote intestinal and organismal health. Although commensal organisms promote health, enteric pathogens, including a diverse plethora of enteric viruses, cause acute and chronic diseases. The barrier epithelium plays fundamental roles in immune defenses against enteric viral infections by integrating diverse signals, including those from the microbiota, to prevent disease. Importantly, many model systems have contributed to our understanding of this complex interface. This review will focus on the antiviral mechanisms at play within the intestinal epithelium and how these responses are shaped by the microbiota.

Enteric Viral Co-Infections: Pathogenesis and Perspective

“…Insect models, including the fruit fly D. melanogaster, can be used to study oral infection by bacterial and viral pathogens in well-characterized, fast-growing, and readily genetically-manipulatable hosts [179][180][181]. Drosophila C virus, related to mammalian enteric picornaviruses, and Flock House Virus, a persistent RNA virus, are natural enteric viral infections in D. melanogaster.…”

“…The nematode C. elegans is the model organism with the most biologically simple intestine, comprised of just 20 clonal enterocytes [181]. C. elegans has a number of advantages, as it has a rapid generation time and can be efficiently screened using forward-and reverse-genetic, as well as drug or small molecule screening approaches.…”

The predicted bZIP transcription factor ZIP-1 promotes resistance to intracellular infection in Caenorhabditis elegans

“…Most studies of antiviral immunity in invertebrates have focused on anti-viral RNAi, and less is known about transcriptional responses to intracellular infection in either of the two major invertebrate model systems, Drosophila melanogaster or C. elegans (24)(25)(26). The IPR in C. elegans is a common transcriptional response that is induced independently by both virus and microsporidia infection, as well as by specific physiological perturbations such as proteotoxic stress (11)(12)(13).…”

Gut Susceptibility to Viral Invasion: Contributing Roles of Diet, Microbiota and Enteric Nervous System to Mucosal Barrier Preservation

“…In the gut, the sensors RIG-I, MDA-5 and NLRP6 activate type III interferons upon virus detection, which stimulate responses that act locally on the epithelial layer. TLR3, on the other hand, indirectly activates type I interferon (IFN) responses, which are active in the lamina propria [ 36 ]. IFNs can be released from infected cells and signal to neighboring cells, inducing an antiviral state that decreases their susceptibility to infection.…”