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Depot medroxyprogesterone acetate (DMPA) enhances susceptibility and increases the window of vulnerability to HIV-1 in humanized mice.
- Source :
-
Scientific reports [Sci Rep] 2021 Feb 16; Vol. 11 (1), pp. 3894. Date of Electronic Publication: 2021 Feb 16. - Publication Year :
- 2021
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Abstract
- The progestin-based hormonal contraceptive Depot Medroxyprogesterone Acetate (DMPA) is widely used in sub-Saharan Africa, where HIV-1 is endemic. Meta-analyses have shown that women using DMPA are 40% more likely than women not using hormonal contraceptives to acquire Human Immunodeficiency Virus (HIV-1). Therefore understanding how DMPA increases susceptibility to HIV-1 is an important public health issue. Using C57BL/6 mice and our previously optimized humanized mouse model (NOD-Rag1 <superscript>tm1Mom</superscript> Il2rg <superscript>tm1Wjl</superscript> transplanted with hCD34-enriched hematopoietic stem cells; Hu-mice) where peripheral blood and tissues are reconstituted by human immune cells, we assessed how DMPA affected mucosal barrier function, HIV-1 susceptibility, viral titres, and target cells compared to mice in the diestrus phase of the estrous cycle, when endogenous progesterone is highest. We found that DMPA enhanced FITC-dextran dye leakage from the vaginal tract into the systemic circulation, enhanced target cells (hCD68+ macrophages, hCD4+ T cells) in the vaginal tract and peripheral blood (hCD45+hCD3+hCD4+hCCR5+ T cells), increased the rate of intravaginal HIV-1 infection, extended the window of vulnerability, and lowered vaginal viral titres following infection. These findings suggest DMPA may enhance susceptibility to HIV-1 in Hu-mice by impairing the vaginal epithelial barrier, increasing vaginal target cells (including macrophages), and extending the period of time during which Hu-mice are susceptible to infection; mechanisms that might also affect HIV-1 susceptibility in women.
- Subjects :
- Animals
Cytokines metabolism
Delayed-Action Preparations
Disease Susceptibility chemically induced
Female
Humans
Infant, Newborn
Macrophages
Mice
Mice, Inbred C57BL
Vagina immunology
Vagina metabolism
Vagina virology
Contraceptive Agents, Hormonal adverse effects
HIV-1
Host-Pathogen Interactions drug effects
Medroxyprogesterone Acetate adverse effects
Vagina drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33594113
- Full Text :
- https://doi.org/10.1038/s41598-021-83242-9