Integrins alpha2beta1 and alpha4beta1 can mediate SA11 rotavirus attachment and entry into cells.
Most mammalian rotaviruses contain tripeptide amino acid sequences in outer capsid proteins VP4 and VP7 which have been shown to act as ligands for integrins alpha2beta1 and alpha4beta1. Peptides containing these sequences and monoclonal antibodies directed to these integrins block rotavirus infection of cells. Here we report that SA11 rotavirus binding to and infection of K562 cells expressing alpha2beta1 or alpha4beta1 integrins via transfection is increased over virus binding to and infection of cells transfected with alpha3 integrin or parent cells. The increased binding and growth were specifically blocked by a monoclonal antibody to the transfected integrin subunit but not by irrelevant antibodies. In our experiments, integrin activation with phorbol ester did not affect virus binding to cells. However, phorbol ester treatment of K562 parent and transfected cells induced endogenous gene expression of alpha2beta1 integrin, which was detectable by flow cytometry 16 h after treatment and quantitatively correlated with the increased level of SA11 virus growth observed after this time. Virus binding to K562 cells treated with phorbol ester 24 h previously and expressing alpha2beta1 was elevated over binding to control cells and was specifically blocked by the anti-alpha2 monoclonal antibody AK7. Virus growth in alpha4-transfected K562 cells which had also been induced to express alpha2beta1 integrin with phorbol ester occurred at a level approaching that in the permissive MA104 cell line. We therefore have demonstrated that two integrins, alpha2beta1 and alpha4beta1, are capable of acting as cellular receptors for SA11 rotavirus.
Hewish
M J
MJ
Department of Microbiology and Immunology, The University of Melbourne, Parkville 3052, Victoria, Australia.
Takada
Y
Y
Coulson
B S
BS
D000911:Antibodies, Monoclonal / Q000276:immunology; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D020014:K562 Cells; D008561:Membrane Fusion / Q000502:physiology*; D038981:Receptors, Collagen; D016201:Receptors, Lymphocyte Homing / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D012401:Rotavirus / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D039041:Integrin alpha4beta1; D016023:Integrins; D038981:Receptors, Collagen; D016201:Receptors, Lymphocyte Homing; D013755:Tetradecanoylphorbol Acetate