The Spike Protein VP4 Defines the Endocytic Pathway Used by Rotavirus To Enter MA104 Cells

Díaz-Salinas, Marco A.; Romero, Pedro; Espinosa, Rafaela; Hoshino, Yasutaka; López, Susana

doi:10.1128/jvi.02086-12

Cited by 46 publications

(56 citation statements)

References 55 publications

(71 reference statements)

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“…Rotavirus usage of GM1 shows a possible association with internalization by clathrin-mediated endocytosis (Tables 1 and 2). MA104 cell entry by Wa, DS-1, UK, and TFR-41 is blocked by treatments that inhibit clathrin-mediated endocytosis and alter endosomal pH, suggesting that they utilize a pathway that includes clathrinmediated endocytosis (11,12). UK VP4 is sufficient to direct rotavirus internalization by this pathway (12).…”

Section: Discussionmentioning

confidence: 99%

“…Rotavirus recognition of ␣2␤1 does not correlate with proposed rotavirus internalization routes (Tables 1 and 2) (11). However, ␣2␤1 recognition might affect the entry process for some rotaviruses, such as the laboratory-derived Nar 3 variant of RRV that no longer depends on terminal Sia for infection (12). Rotavirus usage of GM1 shows a possible association with internalization by clathrin-mediated endocytosis (Tables 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

“…During rotavirus-cell attachment and entry, activated VP4 undergoes a major conformational change that facilitates membrane disruption by VP5* hydrophobic domains (9,10). VP4 may define rotavirus internalization, which commonly but not universally appears to involve clathrin-mediated endocytosis (11)(12)(13).…”

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confidence: 99%

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Relative Roles of GM1 Ganglioside, N -Acylneuraminic Acids, and α2β1 Integrin in Mediating Rotavirus Infection

Fleming

Böhm

Dang

et al. 2014

J Virol

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N-acetyl-and N-glycolylneuraminic acids (Sia) and ␣2␤1 integrin are frequently used by rotaviruses as cellular receptors through recognition by virion spike protein VP4. The VP4 subunit VP8*, derived from Wa rotavirus, binds the internal N-acetylneuraminic acid on ganglioside GM1. Wa infection is increased by enhanced internal Sia access following terminal Sia removal from main glycan chains with sialidase. The GM1 ligand cholera toxin B (CTB) reduces Wa infectivity. Here, we found sialidase treatment increased cellular GM1 availability and the infectivity of several other human (including RV-3) and animal rotaviruses, typically rendering them susceptible to methyl ␣-D-N-acetylneuraminide treatment, but did not alter ␣2␤1 usage. CTB reduced the infectivity of these viruses. Aceramido-GM1 inhibited Wa and RV-3 infectivity in untreated and sialidasetreated cells, and GM1 supplementation increased their infectivity, demonstrating the importance of GM1 for infection. Wa recognition of ␣2␤1 and internal Sia were at least partially independent. Rotavirus usage of GM1 was mapped to VP4 using virus reassortants, and RV-3 VP8* bound aceramido-GM1 by saturation transfer difference nuclear magnetic resonance (STD NMR). Most rotaviruses recognizing terminal Sia did not use GM1, including RRV. RRV VP8* interacted minimally with aceramido-GM1 by STD NMR. Unusually, TFR-41 rotavirus infectivity depended upon terminal Sia and GM1. Competition of CTB, Sia, and/or aceramido-GM1 with cell binding by VP8* from representative rotaviruses showed that rotavirus Sia and GM1 preferences resulted from VP8*-cell binding. Our major finding is that infection by human rotaviruses of commonly occurring VP4 serotypes involves VP8* binding to cell surface GM1 glycan, typically including the internal N-acetylneuraminic acid. IMPORTANCERotaviruses, the major cause of severe infantile gastroenteritis, recognize cell surface receptors through virus spike protein VP4. Several animal rotaviruses are known to bind sialic acids at the termini of main carbohydrate chains. Conversely, only a single human rotavirus is known to bind sialic acid. Interestingly, VP4 of this rotavirus bound to sialic acid that forms a branch on the main carbohydrate chain of the GM1 ganglioside. Here, we use several techniques to demonstrate that other human rotaviruses exhibit similar GM1 usage properties. Furthermore, binding by VP4 to cell surface GM1, involving branched sialic acid recognition, is shown to facilitate infection. In contrast, most animal rotaviruses that bind terminal sialic acids did not utilize GM1 for VP4 cell binding or infection. These studies support a significant role for GM1 in mediating host cell invasion by human rotaviruses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Relative Roles of GM1 Ganglioside, N -Acylneuraminic Acids, and α2β1 Integrin in Mediating Rotavirus Infection

Fleming

Böhm

Dang

et al. 2014

J Virol

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“…Our findings that DBN1 deficiency results in an increase in the entry of RV and VSV, both of which are known to depend on the host GTPase dynamin for endocytosis (21,23) led us to ask whether DBN1 might play a more general role in regulating dynamin-mediated endocytosis. Consistent with this hypothesis, the uptake of fluorescently labeled transferrin, a well-studied ligand of classical clathrin-mediated endocytosis (24), was enhanced in the absence of DBN1: Whereas no transferrin was detected in WT cells, cytoplasmic transferrin signal was visible at 10 min and became more evident at 20 min postincubation in DBN1-deficient cells (Fig.…”

Section: Dbn1 Negatively Regulates the Endocytosis Of Dynamin-dependentmentioning

confidence: 99%

“…RV entry relies on VP4 binding to surface receptors, triggering conformational changes that allow the virus particles to be internalized into the cells in a dynamin-dependent route (21). To examine whether the initial RV attachment to host cells is affected by the loss of DBN1, we performed a standard virus adsorption assay.…”

Section: Vp4 Interactome Analysis Reveals Multiple Host Cytoskeleton-mentioning

confidence: 99%

Drebrin restricts rotavirus entry by inhibiting dynamin-mediated endocytosis

Ding

Feng

et al. 2017

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

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Despite the wide administration of several effective vaccines, rotavirus (RV) remains the single most important etiological agent of severe diarrhea in infants and young children worldwide, with an annual mortality of over 200,000 people. RV attachment and internalization into target cells is mediated by its outer capsid protein VP4. To better understand the molecular details of RV entry, we performed tandem affinity purification coupled with highresolution mass spectrometry to map the host proteins that interact with VP4. We identified an actin-binding protein, drebrin (DBN1), that coprecipitates and colocalizes with VP4 during RV infection. Importantly, blocking DBN1 function by siRNA silencing, CRISPR knockout (KO), or chemical inhibition significantly increased host cell susceptibility to RV infection. Dbn1 KO mice exhibited higher incidence of diarrhea and more viral antigen shedding in their stool samples compared with the wild-type littermates. In addition, we found that uptake of other dynamin-dependent cargos, including transferrin, cholera toxin, and multiple viruses, was also enhanced in DBN1-deficient cells. Inhibition of cortactin or dynamin-2 abrogated the increased virus entry observed in DBN1-deficient cells, suggesting that DBN1 suppresses dynamin-mediated endocytosis via interaction with cortactin. Our study unveiled an unexpected role of DBN1 in restricting the entry of RV and other viruses into host cells and more broadly to function as a crucial negative regulator of diverse dynamin-dependent endocytic pathways.drebrin | rotavirus | endocytosis

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Sialoglycovirology of Lectins: Sialyl Glycan Binding of Enveloped and Non-enveloped Viruses

Sriwilaijaroen

Suzuki

2020

Methods in Molecular Biology

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On the cell sur "face", sialoglycoconjugates act as receptionists that have an important role in the first step of various cellular processes that bridge communication between the cell and its environment. Loss of Sia production can cause the developmental of defects and lethality in most animals; hence, animal cells are less prone to evolution of resistance to interactions by rapidly evolved Sia-binding viruses. Obligative intracellular viruses mostly have rapid evolution that allows escape from host immunity, leading to an epidemic variant, and that allows emergence of a novel strain, occasionally leading to pandemics that cause healthsocial-economic problems. Recently, much attention has been given to the mutual recognition systems via sialosugar chains between viruses and their host cells and there has been rapid growth of the research field "sialoglycovirology." In this chapter, the structural diversity of sialoglycoconjugates is overviewed, and enveloped and non-enveloped viruses that bind to Sia are reviewed. Also, interactions of viral lectins-host Sia receptors, which determine viral transmission, host range, and pathogenesis, are presented. The future direction of new therapeutic routes targeting viral lectins, development of easy-to-use detection methods for diagnosis and monitoring changes in virus binding specificity, and challenges in the development of suitable viruses to use in virus-based therapies for genetic disorders and cancer are discussed.

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The Spike Protein VP4 Defines the Endocytic Pathway Used by Rotavirus To Enter MA104 Cells

Cited by 46 publications

References 55 publications

Relative Roles of GM1 Ganglioside, N -Acylneuraminic Acids, and α2β1 Integrin in Mediating Rotavirus Infection

Relative Roles of GM1 Ganglioside, N -Acylneuraminic Acids, and α2β1 Integrin in Mediating Rotavirus Infection

Drebrin restricts rotavirus entry by inhibiting dynamin-mediated endocytosis

Sialoglycovirology of Lectins: Sialyl Glycan Binding of Enveloped and Non-enveloped Viruses

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