Trends in Microbiology
Multistep entry of rotavirus into cells: a Versaillesque dance
Section snippets
Rotaviruses
Rotaviruses are the leading etiologic agent of severe diarrheal disease in infants and young children worldwide, being responsible for an estimated 500 000 deaths each year [10]; therefore, there is an urgent need to develop effective vaccination and therapeutic strategies to combat these viruses. Fundamental for these developments is a thorough basic understanding of the molecular mechanisms that rotaviruses use to interact with their host cell and replicate.
Rotavirus particles consist of
Rotavirus receptors
It is generally accepted that N-acetylneuraminic acid, also known as sialic acid (SA), is required by some animal rotavirus strains to attach to the cell surface. The infectivity of these strains is greatly diminished by the treatment of cells with neuraminidase (NA); consequently, these strains are NA-sensitive. By contrast, many animal strains and most strains isolated from humans are NA-resistant [15]; however, this does not mean that these strains do not use SA for cell attachment because
Virus–receptor interactions
Several lines of evidence suggest that rotaviruses interact sequentially with several cell surface molecules to enter the cell, using different domains of the virus surface proteins VP4 and VP7 during this process 12, 21, 23, 24, 25, 26, 27, 28, 29, 30. This evidence has been obtained through: (i) a rotavirus competition infection assay that detects virus competition at both binding and post-binding steps [28]; (ii) the characterization of a mutant virus that binds to the cell surface with a
Role of lipid rafts in virus cell entry
The infectivity of rotaviruses is partially blocked by metabolic inhibitors of N-glycosylation and glycolipid synthesis, and is also severely impaired by the depletion of cholesterol from the cellular membrane [43]. On the basis of these findings it was suggested that sphingolipid- and cholesterol-enriched membrane lipid microdomains, usually referred to as lipid rafts (Box 2) [44], might be involved in the entry of rotaviruses into the cell 27, 43, 45. The participation of lipid rafts in
Mechanism of rotavirus cell entry
Early electron microscopy studies of rotavirus-infected cells suggested endocytosis as the virus internalization pathway. However, it was later shown that rotavirus infectivity is not inhibited either by preventing the acidification of endosomes or by drugs that block the intracellular traffic of endocytic vesicles [9]. Direct cell membrane penetration has also been postulated as the mechanism of virus entry on the basis of electron microscopy data and on the observation that rotavirus
Concluding remarks
The recent advances in understanding the early interactions of rotavirus with its host cell have been fueled by the identification of rotavirus cell receptors. Progress in understanding plasma membrane organization, the definition of different types of endocytosis and the application of cryo-electron microscopy to study virus structure, have also been crucial for this purpose. The data presented here indicate the existence of several rotavirus receptors, some of which interact sequentially with
Acknowledgements
We would like to thank U. Desselberger for critical reading of the manuscript and for valuable suggestions and comments, and also P. Isa and E. Méndez for helpful discussions on the manuscript. We appreciate the support by B.V.V. Prasad for providing the cryo-electron microscopy images of the virus. We apologize to colleagues whose work has not have been cited in full owing to length constraints. Work on rotavirus cell entry in our laboratories is supported by grants 55003662 and 55000613 from
References (67)
Receptors and immune sensors: the complex entry path of human cytomegalovirus
Trends Cell Biol.
(2004)- et al.
Lipid raft microdomains: key sites for coxsackievirus A9 infectious cycle
Virology
(2003) - et al.
Virus yoga: the role of flexibility in virus host cell recognition
Trends Microbiol.
(2004) Virus interactions with mucosal surfaces: alternative receptors, alternative pathways
Curr. Opin. Microbiol.
(2003)Rotavirus infection of MA104 cells is inhibited by Ricinus lectin and separately expressed single binding domains
Virology
(2000)Integrin alpha2beta1 mediates the cell attachment of the rotavirus neuraminidase-resistant variant nar3
Virology
(2000)Molecular biology of rotavirus cell entry
Arch. Med. Res.
(2002)- et al.
Attachment and post-attachment receptors for rotavirus
Entry of rotaviruses is a multistep process
Virology
(1999)The VP8 fragment of VP4 is the rhesus rotavirus hemagglutinin
Virology
(1991)
Localization of membrane permeabilization and receptor binding sites on the VP4 hemagglutinin of rotavirus: implications for cell entry
J. Mol. Biol.
Selection of rotavirus VP4 cell receptor binding domains for MA104 cells using a phage display library
J. Virol. Methods
Dynamin at the actin-membrane interface
Curr. Opin. Cell Biol.
Cell receptors involved in adenovirus entry
Virology
Rotavirus infectious particles use lipid rafts during replication for transport to the cell surface in vitro and in vivo
Virology
Integrins: bidirectional, allosteric signaling machines
Cell
Integrins: versatility, modulation, and signaling in cell adhesion
Cell
Cell surface receptors, virus entry and tropism of primate lentiviruses
J. Gen. Virol.
Entry of viruses through the epithelial barrier: pathogenic trickery
Nat. Rev. Mol. Cell Biol.
Virus receptors: binding, adhesion strengthening, and changes in viral structure
J. Virol.
The entry of entry inhibitors: a fusion of science and medicine
Proc. Natl. Acad. Sci. U. S. A.
Rotaviruses and their replication
Global illness and deaths caused by rotavirus disease in children
Emerg. Infect. Dis.
Trypsin cleavage stabilizes the rotavirus VP4 spike
J. Virol.
Integrin-using rotaviruses bind alpha2beta1 integrin alpha2 I domain via VP4 DGE sequence and recognize alphaXbeta2 and alphaVbeta3 by using VP7 during cell entry
J. Virol.
A lymphatic mechanism of rotavirus extraintestinal spread in the neonatal mouse
J. Virol.
VLA-2 (alpha2beta1) integrin promotes rotavirus entry into cells but is not necessary for rotavirus attachment
J. Virol.
Human and most animal rotavirus strains do not require the presence of sialic acid on the cell surface for efficient infectivity
J. Gen. Virol.
Glycosphingolipid binding specificities of rotavirus: identification of a sialic acid-binding epitope
J. Virol.
Initial interaction of rotavirus strains with N-acetylneuraminic (sialic) acid residues on the cell surface correlates with VP4 genotype, not species of origin
J. Virol.
Structure and function of a ganglioside receptor for porcine rotavirus
J. Virol.
Ganglioside GM1a on the cell surface is involved in the infection by human rotavirus KUN and MO strains1
J. Biochem. (Tokyo)
Rotavirus contains integrin ligand sequences and a disintegrin-like domain that are implicated in virus entry into cells
Proc. Natl. Acad. Sci. U. S. A.
Cited by (170)
Evaluation of in vitro antirotaviral activity of lactoferrin from different species using a human intestinal model
2024, International Dairy JournalIntegrin β1 is a key determinant of the expression of angiotensin-converting enzyme 2 (ACE2) in the kidney epithelial cells.
2023, European Journal of Cell BiologyEmerging viruses: Cross-species transmission of coronaviruses, filoviruses, henipaviruses, and rotaviruses from bats
2022, Cell ReportsCitation Excerpt :Host factors or cellular receptors that mediate RVs’ successful infection are also diverse. Some host cell surface molecules, such as heat shock cognate protein 70 and integrins, have been identified as potential RV receptors (Lopez and Arias, 2004). Previous studies have shown that some RVs recognize sialic acid-containing glycoconjugates and are NA sensitive, but the majority of human and animal RVs are sialidase insensitive (Banda et al., 2009; Ciarlet et al., 2002).
Gastrointestinal Tract Infections: Viruses
2022, Encyclopedia of Infection and ImmunityRotavirus research: 2014–2020
2021, Virus ResearchViral Replication Cycle
2020, Encyclopedia of Virology: Volume 1-5, Fourth Edition