Molecular biology of rotavirus cell entry.
Rotaviruses, the leading cause of severe dehydrating diarrhea in infants and young children worldwide, are non-enveloped viruses formed by three concentric layers of protein that enclose a genome of double-stranded RNA. The entry of rotaviruses into epithelial cells appears to be a multistep process during which at least three contacts between the virus and cell receptors occur. Different rotavirus strains display different requirements to infect cells. Some strains depend on the presence of sialic acid on the cell surface; however, interaction with a sialic acid-containing receptor does not seem to be essential, because variants that no longer need sialic acid to infect the cells can be isolated from sialic acid-dependent strains. Comparative characterization of the sialic acid-dependent rotavirus strain RRV, its neuraminidase-resistant variant nar3, and the human rotavirus strain Wa have allowed to show that alpha2beta1 integrin is used by nar3 as its primary cell attachment site, and by RRV in a second interaction subsequent to its initial contact with a sialic acid-containing cell receptor. These first two interactions are mediated by the virus spike protein VP4. After attaching to the cell, all three strains interact with integrin alphaVbeta3 and protein hsc70, interactions perhaps important for the virus to penetrate into the cell's interior. The cell molecules proposed to serve as rotavirus receptors have been found associated with cholesterol and glycosphingolipid-enriched lipid microdomains, and disorganization of these domains greatly inhibits rotavirus infectivity. We propose that the functional rotavirus receptor is a complex of several cell molecules most likely immersed in plasma membrane lipid microdomains.
Arias
Carlos F
CF
Departamento de Genética y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico. arias@ibt.unam.mx
Isa
Pavel
P
Guerrero
Carlos A
CA
Méndez
Ernesto
E
Zárate
Selene
S
López
Tomás
T
Espinosa
Rafaela
R
Romero
Pedro
P
López
Susana
S
D036022:Capsid Proteins / Q000378:metabolism; D002460:Cell Line; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006389:Hemagglutinins, Viral / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D021962:Membrane Microdomains; D008954:Models, Biological; D038981:Receptors, Collagen / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D012401:Rotavirus / Q000472:pathogenicity* / Q000502:physiology* / Q000648:ultrastructure; D012400:Rotavirus Infections / Q000821:virology*
D036022:Capsid Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D006389:Hemagglutinins, Viral; D039302:Integrin alphaVbeta3; D038981:Receptors, Collagen; D011991:Receptors, Virus