Astrovirus Increases Epithelial Barrier Permeability Independently of Viral Replication

Abstract

Astrovirus infection in a variety of species results in an age-dependent diarrhea; however, the means by which astroviruses cause diarrhea remain unknown. Studies of astrovirus-infected humans and turkeys have demonstrated few histological changes and little inflammation during infection, suggesting that intestinal damage or an overzealous immune response is not the primary mediator of astrovirus diarrhea. An alternative contributor to diarrhea is increased intestinal barrier permeability. Here, we demonstrate that astrovirus increases barrier permeability in a Caco-2 cell culture model system following apical infection. Increased permeability correlated with disruption of the tight-junction protein occludin and decreased the number of actin stress fibers in the absence of cell death. Additionally, permeability was increased when monolayers were treated with UV-inactivated virus or purified recombinant human astrovirus serotype 1 capsid in the form of virus-like particles. Together, these results demonstrate that astrovirus-induced permeability occurs independently of viral replication and is modulated by the capsid protein, a property apparently unique to astroviruses. Based on these data, we propose that the capsid contributes to diarrhea in vivo.

HIV-1 impairs human retinal pigment epithelial barrier function: possible association with the pathogenesis of HIV-associated retinopathy

“…17,[38][39][40][41] Other viruses, such as rotavirus and astrovirus, as well as some bacteria, are known to increase intestinal permeability by disrupting tight junctions as part of their pathogenesis. [21][22][23] Here we show that HIV-1 could also induce disruption of tight junction structures in HRPE cells. Notably, we used HIV-1 in the in vitro experiments at a high level resembling the high viral load in the HIV-1-infected patients in the acute phase of infection or in AIDS stage, 42 reflecting the facts that viruses might cause this ocular pathological abnormality at either early phase of infection or the late stage of infection.…”

“…17,18,20 Viruses, such as rotavirus and astrovirus, as well as bacteria, such as enteropathogenic E. coli and C. difficile, are known to increase intestinal permeability by disrupting tight junctions to more easily invade the host. [21][22][23] Although HIV-1 has been found in various ocular fluids, including tears, aqueous humor, subretinal fluids, or vitreous body, [24][25][26][27] it is not clear how HIV-1 in ocular fluids crosses the HRPE and penetrates the inner retina. In vitro cell culture models are valuable tools for studying the physiology and pathophysiology of human naive tissue, particularly under circumstances where access to fresh sample is limited.…”

HIV Exposure to the Epithelia in Ectocervical and Colon Tissues Induces Inflammatory Cytokines Without Tight Junction Disruption

“…10 Various pathogenic organisms such as rotavirus, astrovirus, and Escherichia coli have developed strategies to disrupt the TJ, leading to pathogenic conditions characterized by increased intestinal permeability. 11,12 TJ disruption and a decrease in transepithelial electrical resistance have been observed in human primary endometrial cells and intestinal cell lines after exposure to HIV. 10 However, very little data are available in the literature studying the effect of HIV on epithelial TJ in human ectocervical and rectal/colonic tissues, which are more indicative of in vivo conditions.…”

Astrovirus Pathogenesis

“…Disruptions of the tight junction can result in altered ion and/or solute exchange, increasing fluid to the lumen of the intestine and inducing diarrhea. Astrovirus has been shown to increase epithelial cell permeability upon infection of Caco-2 cells in vitro, possibly due to a reduction in actin fibers [30], reduction of occludin from the junctional complex [30], and redistribution of e-cadherin 24 h post-infection (hpi; Figure 2). sulfate partially blocked HAstV-8 infectivity of Caco-2 cells [66].…”

“…Previous studies demonstrated that HAstVs increase epithelial cell permeability by disrupting cellular tight junctional complexes [30]. Since the intestinal tract depends on tight junctions to separate the lumen from the basal lamina, the loss of integrity increases ion, solute, and water trafficking across the compartments, reducing the ability of the intestine to reabsorb water solute, and water trafficking across the compartments, reducing the ability of the intestine to reabsorb water and nutrients, leading to diarrhea.…”