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.