An increase in the understanding of the mechanisms of male-to-female sexual transmission is the long-term goal of this proposal which can be used to facilitate the development of microbicides and therapies designed to treat the early events of HIV infection. Although mucosal T cells and Langerhans cells have been identified as potential early targets of infection in the female genital tract how the virus gains access to these target cells after traversing the epithelial barriers remains a mystery. To gain insights into this process it is being proposed to utilize a new technology that allows the identification of individual virions of HIV in tissue. The Hope Lab has previously validated this system using ectocervical and endocervical tissue explants and bioengineered epithelial culture systems. However, these types of systems only attempt to mimic what takes place in vivo. It is now time to extend these studies to an animal model for female-to-male sexual transmission. The most characterized of these systems is the rhesus macaque model using SIV modified to use the HIV envelope protein (SHIV). The proposal seeks to fund experimentation to characterize the interaction of HIV with the rhesus macaque female genital tract and provide insights into how HIV gains access to target cells in the vaginal mucosa and those cells first infected. These studies will identify portions of the female genital tract that are less efficient as barriers to HIV entering the underlying tissue. They will also identify the potential interaction of HIV with target cells in the vaginal mucosa and possibly give insight into what cells are infected primarily. They may also identify the interaction of HIV with cellular compartments that will provide insights into the mechanisms of how HIV can enter and move within the tissue. HUMAN

Public Health Relevance

Therefore, these proposed studies are highly relevant to the request for applications because a better understanding of the mechanisms of male-to-female sexual transmission can be used facilitate the development of microbicides and therapies designed to treat the early events of HIV infection (peritransmission events).

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI077321-04
Application #
8197331
Study Section
Special Emphasis Panel (ZRG1-IMM-L (29))
Program Officer
Adger-Johnson, Diane S
Project Start
2008-12-01
Project End
2012-11-30
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
4
Fiscal Year
2012
Total Cost
$29,170
Indirect Cost
Name
Northwestern University at Chicago
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Carias, Ann M; McCoombe, Scott; McRaven, Michael et al. (2013) Defining the interaction of HIV-1 with the mucosal barriers of the female reproductive tract. J Virol 87:11388-400