Expression of the alpha6 integrin confers papillomavirus binding upon receptor-negative B-cells.
Papillomaviruses (PV) bind to a wide range of cell lines in a specific and saturable manner. We have recently identified a candidate receptor for papillomavirus as the alpha6 integrin (Evander et al., J. Virol. 71, 2449-2456, 1997). We have further investigated the role the alpha6 integrin plays in PV binding. Here we show that the cells expressing the alpha6 integrin, partnered with either the beta4 integrin or the beta1 integrin, are equally able to bind PV HPV6b L1 virus-like particles, indicating that the beta partner does not play a major role in virus binding. In order to provide definitive evidence that the alpha6 integrin is required for PV binding we undertook to genetically complement the receptor-negative B-cell line DG75 by expressing the human alpha6A gene. The transduction of the alpha6 integrin gene into DG75 cells results in the cell surface expression of the alpha6 protein and this expression confers upon DG75 cells the ability to bind laminin, a normal ligand for alpha6 integrin. Furthermore, the alpha6 protein is partnered with the beta1 integrin in DG75 cells. Finally, we show that the DG75-alpha6 cells were able to bind papillomavirus VLPs and this binding was inhibited by a functionally blocking anti-alpha6 antibody. Together these data indicate that the alpha6 integrin is a primary cell receptor for papillomaviruses and is both necessary and sufficient for PV binding.
McMillan
N A
NA
Department of Medicine, University of Queensland, Brisbane, Australia. nmcmillan@medicin.pa.uq.edu.au
Payne
E
E
Frazer
I H
IH
Evander
M
M
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology*; D001665:Binding Sites; D019556:COS Cells; D005434:Flow Cytometry; D006801:Humans; D039503:Integrin alpha6; D027383:Papillomaviridae / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology*; D014779:Virus Replication
D015703:Antigens, CD; D039503:Integrin alpha6; D011991:Receptors, Virus