Laryngeal papillomatosis is a Human Papillomavirus (HPV) mediated disease characterized by multiple recurrences and frequent surgeries to maintain an airway. We have found that these infected cells have an impaired ability to present antigen to circulating CD8 T cells. TAP-1 (the Transporter Associated with Antigen Presentation) appeared to be reduced in laryngeal papillomatosis (HPV type 6111). Intriguing new results have lead us to postulate that this key transporter responsible for antigen presentation may not be lacking, but rather, because of an interaction with the E7 viral protein, TAP-1 is unavailable. This interaction imparts a functional consequence: purified HPV 11 E7 protein inhibited ATP-dependent peptide transport in vitro. The TAP-1 E7 interaction observed in HPV 11 seems to occur with HPV 16 as well, according to preliminary immunoprecipitation data, which has lead us to our hypothesis: we hypothesize that one of the conserved domains of E7 interact with TAP-1 and functionally disables it. This application has three specific aims to test the hypothesis: 1. To determine the critical region of HPV 11 E7 necessary for a physical interaction with TAP-1 and analyze whether this critical region also imparts functional inhibition of the transporter. 2. To determine if polymorphisms of TAP-1 or E7 can partially account for variations in disease susceptibility. 3. To determine whether the interaction between TAP-1 and E7 in naturally occurring infections sufficient to result in a loss of peptide transport and whether this loss correlates with viral protein load and the patients clinical course.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
6R03DC005150-02
Application #
6603273
Study Section
Special Emphasis Panel (ZDC1-SRB-O (28))
Program Officer
Shekim, Lana O
Project Start
2002-05-01
Project End
2005-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
2
Fiscal Year
2003
Total Cost
$79,000
Indirect Cost
Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
110565913
City
Manhasset
State
NY
Country
United States
Zip Code
11030