Browsing by Subject "Enterovirus Infections"

Now showing 1 - 3 of 3

Open Access
Enteroviruses: A Gut-Wrenching Game of Entry, Detection, and Evasion.
(Viruses, 2019-05-21) Wells, Alexandra I; Coyne, Carolyn B
Enteroviruses are a major source of human disease, particularly in neonates and young children where infections can range from acute, self-limited febrile illness to meningitis, endocarditis, hepatitis, and acute flaccid myelitis. The enterovirus genus includes poliovirus, coxsackieviruses, echoviruses, enterovirus 71, and enterovirus D68. Enteroviruses primarily infect by the fecal-oral route and target the gastrointestinal epithelium early during their life cycles. In addition, spread via the respiratory tract is possible and some enteroviruses such as enterovirus D68 are preferentially spread via this route. Once internalized, enteroviruses are detected by intracellular proteins that recognize common viral features and trigger antiviral innate immune signaling. However, co-evolution of enteroviruses with humans has allowed them to develop strategies to evade detection or disrupt signaling. In this review, we will discuss how enteroviruses infect the gastrointestinal tract, the mechanisms by which cells detect enterovirus infections, and the strategies enteroviruses use to escape this detection.
Open Access
Stem Cell-Derived Models of Viral Infections in the Gastrointestinal Tract.
(Viruses, 2018-03-10) Lanik, Wyatt E; Mara, Madison A; Mihi, Belgacem; Coyne, Carolyn B; Good, Misty
Studies on the intestinal epithelial response to viral infection have previously been limited by the absence of in vitro human intestinal models that recapitulate the multicellular complexity of the gastrointestinal tract. Recent technological advances have led to the development of "mini-intestine" models, which mimic the diverse cellular nature and physiological activity of the small intestine. Utilizing adult or embryonic intestinal tissue, enteroid and organoid systems, respectively, represent an opportunity to effectively model cellular differentiation, proliferation, and interactions that are specific to the specialized environment of the intestine. Enteroid and organoid systems represent a significant advantage over traditional in vitro methods because they model the structure and function of the small intestine while also maintaining the genetic identity of the host. These more physiologic models also allow for novel approaches to investigate the interaction of enteric viruses with the gastrointestinal tract, making them ideal to study the complexities of host-pathogen interactions in this unique cellular environment. This review aims to provide a summary on the use of human enteroid and organoid systems as models to study virus pathogenesis.
Open Access
Unc93b Induces Apoptotic Cell Death and Is Cleaved by Host and Enteroviral Proteases.
(PloS one, 2015-01) Harris, Katharine G; Coyne, Carolyn B
Unc93b is an endoplasmic reticulum (ER)-resident transmembrane protein that serves to bind and traffic toll-like receptors (TLRs) from the ER to their appropriate subcellular locations for ligand sensing. Because of its role in TLR trafficking, Unc93b is necessary for an effective innate immune response to coxsackievirus B3 (CVB), a positive-sense single stranded RNA virus belonging to the enterovirus family. Here, we show that Unc93b is cleaved by a CVB-encoded cysteine protease (3Cpro) during viral replication. Further, we define a role for Unc93b in the induction of apoptotic cell death and show that expression of wild-type Unc93b, but not a mutant incapable of binding TLRs or exiting the ER (H412R), induces apoptosis. Furthermore, we show that cellular caspases activated during apoptosis directly cleave Unc93b. Interestingly, we show that the 3Cpro- and caspase-mediated cleavage of Unc93b both occur within ten amino acids in the distal N-terminus of Unc93b. Mechanistically, neither caspase-mediated nor 3Cpro-mediated cleavage of Unc93b altered its trafficking function, inhibited its role in facilitating TLR3 or TLR8 signaling, or altered its apoptosis-inducing effects. Taken together, our studies show that Unc93b is targeted by both viral- and host cell-specific proteases and identify a function of Unc93b in the induction of apoptotic cell death.