Infection with high risk oncogenic Human Papillomavirus (HPV) 16 and 18 has been identified as the major risk factor for cervical cancer and anal cancer. In order for this to occur, oncogenic HPV first binds to cell surface receptors of basal epithelial cells. Binding may lead to induction of signaling cascades that could mediate the dynamin dependent clathrin/caveolae- mediated endocytosis of the virus which may lead to infection. Subsequent replication of the virus using the host cell machinery may lead to cervical and anal cancer. My long-term objective is to decipher which signal transduction molecules are involved in mediating oncogenic HPV infections upon binding, and to determine if the molecules or their effectors can be used as a broad target strategy in preventing oncogenic HPV infection.
My aims would be to 1.)To determine whether primary binding of HPV to heparan sulfate and complexing to the alpha6 beta4 integrin complex receptor induces the signaling molecules needed to mediate HPV infection. 2.) To identify the signaling molecules needed to mediate the dynamin-dependent endocytosis of HPV infection. To approach this study, I plan to use re-expressed Wild-Type (WT) beta 4 keratinocytes and beta 4 null keratinocytes to determine if the virus receptor interaction in aim 1 is needed for infection.
For Aim 2, 1 plan to show the protein expression of phosphorylated signaling molecules using immunoprecipitation and immunofluorescence techniques. The human papilloma virus infects the cells lining the cervix and anus by binding to the cells, entering them, using their machinery to multiply consequently causing cancer. The goal of our research is to investigate the process by which the virus binds and utilizes the human cells to multiply. Ultimately, our goal is to decipher means of terminating HPV infection thus preventing cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI081515-03
Application #
8034682
Study Section
Special Emphasis Panel (ZRG1-DIG-E (29))
Program Officer
Adger-Johnson, Diane S
Project Start
2009-04-01
Project End
2013-11-30
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
3
Fiscal Year
2011
Total Cost
$42,094
Indirect Cost
Name
Rosalind Franklin University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
069501252
City
North Chicago
State
IL
Country
United States
Zip Code
60064
Abban, Cynthia Y; Meneses, Patricio I (2010) Usage of heparan sulfate, integrins, and FAK in HPV16 infection. Virology 403:1-16