Interaction of human papillomavirus type 11 E7 protein with TAP-1 results in the reduction of ATP-dependent peptide transport.
Human papillomaviruses (HPVs) cause benign and malignant epithelial tumors of the respiratory and genital mucosa. We previously reported that recurrent respiratory papillomas caused by HPV 6/11 express low levels of antibody-detectable TAP-1, the protein that transports peptides into the endoplasmic reticulum for assembly and presentation by MHC Class I, and that the extent of TAP-1 immunostaining is inversely related to the frequency of disease recurrence. We have now determined a mechanism for the reduction in TAP-1 detection. Anti-TAP-1 antibody immunoprecipitated very low amounts of protein from papilloma cells. However, immunoprecipitation of calreticulin, another member of the MHC I assembly complex, coprecipitated TAP-1 at levels comparable to those of uninfected cells. Immunoprecipitation of an HPV-positive cell line with either anti-TAP-1 or anti-calreticulin coprecipitated HPV E7 protein. Finally, purified HPV 11 E7 protein inhibited ATP-dependent peptide transport in vitro. We propose that the interaction of E7 with TAP-1 prevents TAP-1 antibody detection and efficient peptide transport, resulting in poor presentation of viral antigen on HPV-infected cells and thus failure to mount an effective immune-mediated prevention of disease recurrence.
Vambutas
A
A
Department of Otolaryngology, The Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, New York 11040, USA.
DeVoti
J
J
Pinn
W
W
Steinberg
B M
BM
Bonagura
V R
VR
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000502:physiology; D017951:Antigen Presentation; D006801:Humans; D007822:Laryngeal Neoplasms / Q000276:immunology / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism* / Q000494:pharmacology*; D010212:Papilloma / Q000276:immunology / Q000378:metabolism*; D027383:Papillomaviridae / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D021381:Protein Transport; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000276:immunology / Q000378:metabolism*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D009856:Oncogene Proteins, Viral; D010455:Peptides; C073119:TAP1 protein, human; C062495:oncogene protein E7, Human papillomavirus type 6; D000255:Adenosine Triphosphate