"HIV Susceptibility and Pathogenesis in the Female Genital Tract" is designed to study mechanisms of HIV infection that are unique to women. Its four investigator initiated projects are strongly interactive and focus on HIV in the female genital tract. Project I, Microscopic Analysis of the Interaction of HIV and the Human Female Genital Tract (Thomas Hope, PhD, NWU), studies HIV interaction with tissue and mucous in the female genital tract. Project II, HIV and Female Genital Tract Flora (Greg Spear, PhD, RUMC), studies the effect of bacterial infection in the genital tract on susceptibility to HIV infection. Project III, HIV-Specific Immunity in Highly Exposed Uninfected Women (Richard Novak, MD, UIC and Linda Baum, PhD, RUMC), studies the potential development of protective mucosal immunity that results from sexual exposure to HIV. Project IV, Role of Estrogen in HIV Transmission and Pathogenesis (Lena AI-Harthi, PhD, RUMC), studies the effects of estrogen mediated leukocyte activation and Wnt/p-catenin signaling on HIV transmission. Four cores foster the collaborative interactions between projects. Core A (Administrative Core) is directed by the Program Project PI, Alan Landay, PhD, RUMC. Core B (Clinical Core) directed by Audrey French, MD, Cook County, will provide samples from established cohorts of HIV infected women: the Women's Interagency HIV Study (WIHS), the Women at Heterosexual Risk Cohort (WISH) and HIV infected women from Rwanda (RWISA). When necessary, women of interest from these established cohorts will be recruited to provide additional samples. Core C (Tissue Culture and Virology Laboratory Core) directed by Nell Lurain, PhD, RUMC, will perform experiments with the HIV tissue explant replication model, prepare molecular and virologic reagents, and maintain a specimen repository. Core D (Biostatistics/Epidemiology Core) directed by Elizabeth Golub, PhD, JHU, will help project investigators plan studies and evaluate results. The synergy of effort among projects and cores is evident in aims that require participation of multiple investigators and resources provided by the cores. This PO1 will improve our understanding of factors that enhance or inhibit sexual transmission of HIV and will lead to the development of innovative interventions to prevent HIV.

Public Health Relevance

The 4 projects and 4 cores of this program project will provide novel insights into the pathogenesis of HIV disease in women. All of these studies utilize a novel in vitro explant model that mimics HIV infection in the human female genital tract and samples from patient cohorts. They will provide potentially important information that will lead to the development of new approaches for HIV prevention and therapy in women.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI082971-04
Application #
8319582
Study Section
Special Emphasis Panel (ZAI1-TP-A (J2))
Program Officer
Embry, Alan C
Project Start
2009-09-30
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$2,168,559
Indirect Cost
$396,014
Name
Rush University Medical Center
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
068610245
City
Chicago
State
IL
Country
United States
Zip Code
60612
Archary, Derseree; Liebenberg, Lenine J; Werner, Lise et al. (2015) Randomized Cross-Sectional Study to Compare HIV-1 Specific Antibody and Cytokine Concentrations in Female Genital Secretions Obtained by Menstrual Cup and Cervicovaginal Lavage. PLoS One 10:e0131906
Arslan, Sevim Yildiz; Yu, Yanni; Burdette, Joanne E et al. (2015) Novel three dimensional human endocervix cultures respond to 28-day hormone treatment. Endocrinology 156:1602-9
Tjernlund, Annelie; Carias, Ann M; Andersson, Sonia et al. (2015) Progesterone-based intrauterine device use is associated with a thinner apical layer of the human ectocervical epithelium and a lower ZO-1 mRNA expression. Biol Reprod 92:68
Aziz, Mariam; Mahmood, Fareeha; Mata, Mariana et al. (2015) Development of IgG Mediated Antibody Dependent Cell-mediated Cytotoxicity (ADCC) in the Serum and Genital Mucosa of HIV Seroconverters. J AIDS Clin Res 6:
Mirmonsef, Paria; Modur, Sharada; Burgad, Derick et al. (2015) Exploratory comparison of vaginal glycogen and Lactobacillus levels in premenopausal and postmenopausal women. Menopause 22:702-9
Jarrett, Olamide D; Brady, Kirsten E; Modur, Sharada P et al. (2015) T. vaginalis Infection Is Associated with Increased IL-8 and TNFr1 Levels but with the Absence of CD38 and HLADR Activation in the Cervix of ESN. PLoS One 10:e0130146
Spear, Greg T; McKenna, Mary; Landay, Alan L et al. (2015) Effect of pH on Cleavage of Glycogen by Vaginal Enzymes. PLoS One 10:e0132646
Allen, Shannon A; Carias, Ann M; Anderson, Meegan R et al. (2015) Characterization of the Influence of Semen-Derived Enhancer of Virus Infection on the Interaction of HIV-1 with Female Reproductive Tract Tissues. J Virol 89:5569-80
Mirmonsef, Paria; Hotton, Anna L; Gilbert, Douglas et al. (2014) Free glycogen in vaginal fluids is associated with Lactobacillus colonization and low vaginal pH. PLoS One 9:e102467
Aljawai, Yosra; Richards, Maureen H; Seaton, Melanie S et al. (2014) β-Catenin/TCF-4 signaling regulates susceptibility of macrophages and resistance of monocytes to HIV-1 productive infection. Curr HIV Res 12:164-73

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