Initial Interaction of Rotavirus Strains with
            <i>N</i>
            -Acetylneuraminic (Sialic) Acid Residues on the Cell Surface Correlates with VP4 Genotype, Not Species of Origin

Ciarlet, Max; Ludert, Juan E.; Iturriza‐Gómara, Miren; Liprandi, Ferdinando; Gray, James J.; Desselberger, Ulrich; Estes, Mary K.

doi:10.1128/jvi.76.8.4087-4095.2002

Cited by 90 publications

(159 citation statements)

References 38 publications

(138 reference statements)

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“…c Terminal SA usage (ϩ, Ϫ) determined previously (8) or inferred [(ϩ), (Ϫ)] from identity of P serotype and species of origin with a tested rotavirus strain.…”

Section: Resultsmentioning

confidence: 99%

“…b Serotypes designations are as previously described (8,24,31). P serotype precedes P genotype, which is shown in square brackets.…”

Section: Resultsmentioning

confidence: 99%

“…The integrin independence of P2A and P2B rotaviruses and the integrin usage by both P1A and P1B rotaviruses is not surprising given the close serological and VP4 sequence relationship between viruses within each P serotype. Although both rotavirus usage of integrins and terminal SA binding ability (8) relate to P serotype, integrin usage was independent of SA binding ability. This is consistent with the distinct locations on the virion of the SA-binding region (VP8*), the ␣2␤1-binding region (VP5*), and the regions involved in ␣X␤2 and ␣V␤3 interactions (VP7).…”

Section: Vol 77 2003 Rotaviruses Recognize Integrins Via Vp4 Dge Anmentioning

confidence: 99%

“…Terminal sialic acids (SA) can be used by a few animal strains, including SA11 and RRV (8), but are not essential for infection (55). Infection by the majority of rotaviruses is independent of terminal SA, but it might involve subterminal SA (14,22).…”

mentioning

confidence: 99%

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Integrin-Using Rotaviruses Bind α2β1 Integrin α2 I Domain via VP4 DGE Sequence and Recognize αXβ2 and αVβ3 by Using VP7 during Cell Entry

Graham

Halász

Tan

et al. 2003

J Virol

141

186

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Integrins ␣2␤1, ␣X␤2, and ␣V␤3 have been implicated in rotavirus cell attachment and entry. The virus spike protein VP4 contains the ␣2␤1 ligand sequence DGE at amino acid positions 308 to 310, and the outer capsid protein VP7 contains the ␣X␤2 ligand sequence GPR. To determine the viral proteins and sequences involved and to define the roles of ␣2␤1, ␣X␤2, and ␣V␤3, we analyzed the ability of rotaviruses and their reassortants to use these integrins for cell binding and infection and the effect of peptides DGEA and GPRP on these events. Many laboratory-adapted human, monkey, and bovine viruses used integrins, whereas all porcine viruses were integrin independent. The integrin-using rotavirus strains each interacted with all three integrins. Integrin usage related to VP4 serotype independently of sialic acid usage. Analysis of rotavirus reassortants and assays of virus binding and infectivity in integrin-transfected cells showed that VP4 bound ␣2␤1, and VP7 interacted with ␣X␤2 and ␣V␤3 at a postbinding stage. DGEA inhibited rotavirus binding to ␣2␤1 and infectivity, whereas GPRP binding to ␣X␤2 inhibited infectivity but not binding. The truncated VP5* subunit of VP4, expressed as a glutathione S-transferase fusion protein, bound the expressed ␣2 I domain. Alanine mutagenesis of D308 and G309 in VP5* eliminated VP5* binding to the ␣2 I domain. In a novel process, integrin-using viruses bind the ␣2 I domain of ␣2␤1 via DGE in VP4 and interact with ␣X␤2 (via GPR) and ␣V␤3 by using VP7 to facilitate cell entry and infection.Rotaviruses are leading causes of acute gastroenteritis in human infants and young animals. Their restricted tropism suggests that very specific virus-host cell interactions are necessary to establish infection. The viral spike protein VP4, the major cell attachment protein, is cleaved by trypsin for enhanced infectivity into two subunits, VP5* (60 kDa) and VP8* (28 kDa). VP4 and the major outer capsid protein VP7 independently define serotype specificities. The inner capsid protein VP6 contains group-specific antigenic determinants. Reassortant rotaviruses containing combinations of the 11 double-stranded RNA genes from two parental viruses can be generated (27) which occasionally show unexpected phenotypes due to VP4-VP7 interactions (43).Integrins ␣2␤1, ␣X␤2, and ␣4␤1 were implicated in group A rotavirus cell attachment and entry (11, 23), and ␣V␤3 was proposed to mediate rotavirus cell entry (20). Integrin usage by rotaviruses was discovered when VP5* was shown to contain the type I collagen-derived, ␣2␤1 ligand sequence DGE at amino acids 308 to 310, and the fibrinogen-derived ␣X␤2 integrin ligand sequence GPR was identified in VP7 at amino acids 253 to 255 (11). Peptides containing these viral integrin ligand sequences (GPRP and RDGEE), monoclonal antibodies (MAbs) to ␣2␤1 and MAbs to ␤2, inhibited the infection of monolayers of MA104 and Caco-2 cells by simian rotavirus SA11 and/or human rotavirus RV-5 by 30 to 90% in additive fashion (9, 11). Infectivity blockade in MA104 cell monolayers...

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“…c Terminal SA usage (ϩ, Ϫ) determined previously (8) or inferred [(ϩ), (Ϫ)] from identity of P serotype and species of origin with a tested rotavirus strain.…”

Section: Resultsmentioning

confidence: 99%

“…b Serotypes designations are as previously described (8,24,31). P serotype precedes P genotype, which is shown in square brackets.…”

Section: Resultsmentioning

confidence: 99%

Section: Vol 77 2003 Rotaviruses Recognize Integrins Via Vp4 Dge Anmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Integrin-Using Rotaviruses Bind α2β1 Integrin α2 I Domain via VP4 DGE Sequence and Recognize αXβ2 and αVβ3 by Using VP7 during Cell Entry

Graham

Halász

Tan

et al. 2003

J Virol

141

186

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show abstract

“…Prior to cleavage, the spike-like VP4 projections do not form, and its various domains are probably flexibly linked (6). The VP8* fragment, which forms the "heads" at the tips of a spike, is a lectin-like module that in many strains binds sialic acid (5,10). The VP5* fragment, which forms the spike body, stalk, and foot, is probably the membrane-active element (9,17).…”

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confidence: 99%

A Rotavirus Spike Protein Conformational Intermediate Binds Lipid Bilayers

Trask

Kim

Harrison

et al. 2010

J Virol

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During rotavirus entry, a virion penetrates a host cell membrane, sheds its outer capsid proteins, and releases a transcriptionally active subviral particle into the cytoplasm. VP5*, the rotavirus protein believed to interact with the membrane bilayer, is a tryptic cleavage product of the outer capsid spike protein, VP4. When a rotavirus particle uncoats, VP5* folds back, in a rearrangement that resembles the fusogenic conformational changes in enveloped-virus fusion proteins. We present direct experimental evidence that this rearrangement leads to membrane binding. VP5* does not associate with liposomes when mounted as part of the trypsinprimed spikes on intact virions, nor does it do so after it has folded back into a stably trimeric, low-energy state. But it does bind liposomes when they are added to virions before uncoating, and VP5* rearrangement is then triggered by addition of EDTA. The presence of liposomes during the rearrangement enhances the otherwise inefficient VP5* conformational change. A VP5* fragment, VP5CT, produced from monomeric recombinant VP4 by successive treatments with chymotrypsin and trypsin, also binds liposomes only when the proteolysis proceeds in their presence. A monoclonal antibody that neutralizes infectivity by blocking a postattachment entry event also blocks VP5* liposome association. We propose that VP5* binds lipid bilayers in an intermediate conformational state, analogous to the extended intermediate conformation of enveloped-virus fusion proteins.

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