Infantile enteritis viruses: morphogenesis and morphology

Holmes, Ian; Ruck, B. J.; Bishop, R. F.; Davidson, Garry J.

doi:10.1128/jvi.16.4.937-943.1975

Cited by 94 publications

(2 citation statements)

References 24 publications

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“…Therefore, we next determined whether RV-mediated DGAT1 degradation in HIEs results in phenotypic changes similar to those observed in biopsies from DGAT1-deficient children. Although few histopathological studies of samples from patients with RV infection have been carried out, villus blunting was observed ( 31 ). Since HIEs do not have typical villus structures, villus blunting could not be assessed in HIEs.…”

Section: Resultsmentioning

confidence: 99%

Rotavirus-mediated DGAT1 degradation: A pathophysiological mechanism of viral-induced malabsorptive diarrhea

Liu,

Smith,

Criglar

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Gastroenteritis is among the leading causes of mortality globally in infants and young children, with rotavirus (RV) causing ~258 million episodes of diarrhea and ~128,000 deaths annually in infants and children. RV-induced mechanisms that result in diarrhea are not completely understood, but malabsorption is a contributing factor. RV alters cellular lipid metabolism by inducing lipid droplet (LD) formation as a platform for replication factories named viroplasms. A link between LD formation and gastroenteritis has not been identified. We found that diacylglycerol O-acyltransferase 1 (DGAT1), the terminal step in triacylglycerol synthesis required for LD biogenesis, is degraded in RV-infected cells by a proteasome-mediated mechanism. RV-infected DGAT1-silenced cells show earlier and increased numbers of LD-associated viroplasms per cell that translate into a fourfold-to-fivefold increase in viral yield ( P < 0.05). Interestingly, DGAT1 deficiency in children is associated with diarrhea due to altered trafficking of key ion transporters to the apical brush border of enterocytes. Confocal microscopy and immunoblot analyses of RV-infected cells and DGAT1 −/− human intestinal enteroids (HIEs) show a decrease in expression of nutrient transporters, ion transporters, tight junctional proteins, and cytoskeletal proteins. Increased phospho-eIF2α (eukaryotic initiation factor 2 alpha) in DGAT1 −/− HIEs, and RV-infected cells, indicates a mechanism for malabsorptive diarrhea, namely inhibition of translation of cellular proteins critical for nutrient digestion and intestinal absorption. Our study elucidates a pathophysiological mechanism of RV-induced DGAT1 deficiency by protein degradation that mediates malabsorptive diarrhea, as well as a role for lipid metabolism, in the pathogenesis of gastroenteritis.

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Section: Resultsmentioning

confidence: 99%

Rotavirus-mediated DGAT1 degradation: A pathophysiological mechanism of viral-induced malabsorptive diarrhea

Liu,

Smith,

Criglar

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“…Rotavirus predominantly infects mature enterocytes at the top and middle of the intestinal villi, leading to the vacuolization of enterocytes [ 1 ]. Rotavirus infection and replication in the duodenal mucosa of infants cause shortening and atrophy of the villi, loss of microvilli, mononuclear cell infiltration, distended endoplasmic reticulum, and mitochondrial swelling in enterocytes [ 78 , 79 ]. The suggested mechanisms underlying these findings include virus-mediated apoptosis [ 80 ], NSP4-mediated mislocalization of the ZO-1 tight junction protein [ 81 ], binding to the basement membrane extracellular matrix proteins laminin subunit-β3 and fibronectin [ 82 ], and disruption of normal cellular homeostasis [ 83 ].…”

Section: Proposed Potential Mechanisms Of Rotavirus Infection-associa...mentioning

confidence: 99%

Rotavirus infection-associated central nervous system complications: clinicoradiological features and potential mechanisms

Lee

2022

Clin Exp Pediatr

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Despite the introduction of vaccines in 2006, rotavirus remains one of the most common causes of pediatric gastroenteritis worldwide. While many studies have conclusively shown that rotavirus infection causes gastroenteritis and is associated with various extra-intestinal manifestations including central nervous system (CNS) complications, extra-intestinal manifestations due to rotavirus infection have been relatively overlooked. Rotavirus infectionassociated CNS complications are common in children and present with diverse clinicoradiological features. Rotavirus infection-associated CNS complications can be classified based on clinical features and brain magnetic resonance imaging findings, particularly lesion location on diffusion-weighted imaging. Common clinicoradiological features of rotavirus infection-associated CNS complications include: (1) benign convulsions with mild gastroenteritis; (2) acute encephalopathies/encephalitis, such as mild encephalopathy with a reversible splenial lesion, acute encephalopathy with biphasic seizures and late reduced diffusion, and acute necrotizing encephalopathy; (3) acute cerebellitis; and (4) neonatal rotavirus-associated leukoencephalopathy. The precise mechanism underlying the development of these complications remains unknown despite a number of clinical and laboratory studies. Here we review the diverse clinicoradiological features of rotavirus infection-associated CNS complications and propose a hypothesis of their pathophysiology.

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