Cell surface sialylation affects binding of enterovirus 71 to rhabdomyosarcoma and neuroblastoma cells

Su, Pei Yi; Liu, Yueh Tung; Chang, Hsin Yueh; Huang, Sheng Wen; Wang, Ya Fang; Yu, Chun Keung; Wang, Jen Ren; Chang, Chin-Fu

doi:10.1186/1471-2180-12-162

Cited by 45 publications

(44 citation statements)

References 45 publications

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“…In addition, EV71 can interact with sialylated, desialylated, or deglycosylated SCARB2 (9,15). These findings suggest that sialylation may be a common modification for EV71 receptors, and the removal of sialic acids does not affect the binding of EV71 to receptors.…”

mentioning

confidence: 72%

“…RD cells were harvested and homogenized, and the membrane proteins were obtained as previously described (9). Cells were harvested and homogenized in ice-cold homogenization buffer (20 mM Tris-HCl, pH 7.5, 2.0 mM EDTA, 1.0 mM dithiothreitol [DTT], and protein inhibitor cocktail) using a sonicator (Chrom Tech), and the cell lysate was centrifuged at 90 ϫ g for 10 min to remove the cell debris.…”

Section: Cells and Virusesmentioning

confidence: 99%

“…In addition, PSGL-1 participates in EV71 virus binding but not virus entry and viral RNA release (16). Although EV71 uses multiple receptors (18), none of the antireceptor or antiattachment molecule antibodies can completely abolish the infection of host cells by EV71 (7)(8)(9)(10)(11)(12)18). Undiscovered receptors or cofactors that are involved in the binding and infection of EV71 urgently need to be identified.…”

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confidence: 99%

“…We previously demonstrated that a cell surface monosaccharide, sialic acid, can mediate EV71 binding and infection (9).…”

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confidence: 99%

“…Because virus receptors determine the host range, tissue tropism, and pathogenesis (4-6), the identification of factors that mediate the recognition and/or entry of EV71 to host cells is essential to decipher infection mechanisms. Several receptors or attachment molecules for EV71 have been identified, including scavenger receptor B2 (SCARB2), P-selectin glycoprotein ligand-1 (PSGL-1), sialylated glycoprotein, dendritic cell-specific ICAM 3-grabbing nonintegrin, annexin II, vimentin, and polysaccharide (heparin sulfate) (7)(8)(9)(10)(11)(12)(13). EV71 strains can be divided into different subgenotypes based on sequence homology (14).…”

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confidence: 99%

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Cell Surface Nucleolin Facilitates Enterovirus 71 Binding and Infection

Wang

Huang

et al. 2015

J Virol

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Because the pathogenesis of enterovirus 71 (EV71) remains mostly ambiguous, identifying the factors that mediate viral binding and entry to host cells is indispensable to ultimately uncover the mechanisms that underlie virus infection and pathogenesis. Despite the identification of several receptors/attachment molecules for EV71, the binding, entry, and infection mechanisms of EV71 remain unclear. Herein, we employed glycoproteomic approaches to identify human nucleolin as a novel binding receptor for EV71. Glycoproteins purified by lectin chromatography from the membrane extraction of human cells were treated with sialidase, followed by immunoprecipitation with EV71 particles. Among the 16 proteins identified by tandem mass spectrometry analysis, cell surface nucleolin attracted our attention. We found that EV71 interacted directly with nucleolin via the VP1 capsid protein and that an antinucleolin antibody reduced the binding of EV71 to human cells. In addition, the knockdown of cell surface nucleolin decreased EV71 binding, infection, and production in human cells. Furthermore, the expression of human nucleolin on the cell surface of a mouse cell line increased EV71 binding and conferred EV71 infection and production in the cells. These results strongly indicate that human nucleolin can mediate EV71 binding to and infection of cells. Our findings also demonstrate that the use of glycoproteomic approaches is a reliable methodology to discover novel receptors for pathogens. IMPORTANCEOutbreaks of EV71 have been reported in Asia-Pacific countries and have caused thousands of deaths in young children during the last 2 decades. The discovery of new EV71-interacting molecules to understand the infection mechanism has become an emergent issue. Hence, this study uses glycoproteomic approaches to comprehensively investigate the EV71-interacting glycoproteins. Several EV71-interacting glycoproteins are identified, and the role of cell surface nucleolin in mediating the attachment and entry of EV71 is characterized and validated. Our findings not only indicate a novel target for uncovering the EV71 infection mechanism and anti-EV71 drug discovery but also provide a new strategy for virus receptor identification.

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mentioning

confidence: 72%

Section: Cells and Virusesmentioning

confidence: 99%