The objective is to search for mechanisms by which the female hormones progesterone and estrogen influence vaginal transmission and pathogenesis of SIV in rhesus macaques. In work recently published by this laboratory, progesterone was shown to increase SIV vaginal transmission and thinning of the vaginal epithelium was proposed as one potential mechanism. However affects on immune responses, possible increases in target cells within vaginal tissues, or direct effects on in vivo SIV replication were not studied and are the object of this new application.
Specific aim one individually tests the effects of progesterone and estrogen on SIV vaginal transmission, pathogenesis, and virus-specific immune responses.
Specific aim two tests progesterone and estrogen effects on in vivo pathogenesis after intravenous infection of hormone treated macaques. These studies allow evaluation of two hormones important for female reproductive cycles and allow the study of ovariectomized animals to isolate the effects of virus transmission independent of these hormones. The studies should inform about the potential hazards of female contraceptives and how they may influence virus transmission. In addition basic information will be provided on the effects of female reproductive hormones on virus transmission and viral pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI041952-02
Application #
2673124
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1997-09-01
Project End
2000-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Aaron Diamond AIDS Research Center
Department
Type
DUNS #
786658872
City
New York
State
NY
Country
United States
Zip Code
10016
Smith, Stephen M; Mefford, Megan; Sodora, Donald et al. (2004) Topical estrogen protects against SIV vaginal transmission without evidence of systemic effect. AIDS 18:1637-43
Shacklett, Barbara L; Ling, Binhua; Veazey, Ronald S et al. (2002) Boosting of SIV-specific T cell responses in rhesus macaques that resist repeated intravaginal challenge with SIVmac251. AIDS Res Hum Retroviruses 18:1081-8
Baskin, G B; Smith, S M; Marx, P A (2002) Endometrial hyperplasia, polyps, and adenomyosis associated with unopposed estrogen in rhesus monkeys (Macaca mulatta). Vet Pathol 39:572-5
Xu, Xue-Ming; Carlson, Bradley A; Grimm, Tobias A et al. (2002) Rhesus monkey simian immunodeficiency virus infection as a model for assessing the role of selenium in AIDS. J Acquir Immune Defic Syndr 31:453-63
Parren, P W; Marx, P A; Hessell, A J et al. (2001) Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro. J Virol 75:8340-7