Herpes Simplex Virus type2 and contraception

Medroxyprogesterone acetate and levonorgestrel increase genital mucosal permeability and enhance susceptibility to genital herpes simplex virus type 2 infection

N E Quispe Calla1, R D Vicetti Miguel1, P N Boyaka2, L Hall-Stoodley1, B Kaur3, W Trout4, S D Pavelko1 and T L Cherpes1,4

1. Department of Microbial Infection and Immunity, Columbus, Ohio, USA

2. Department of Veterinary Biosciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA

3. Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio, USA

4.Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio, USA

Depot-medroxyprogesterone acetate (DMPA) is a hormonal contraceptive especially popular in areas with high prevalence of HIV and other sexually transmitted infections (STI). Although observational studies identify DMPA as an important STI risk factor, mechanisms underlying this connection are undefined. Levonorgestrel (LNG) is another progestin used for hormonal contraception, but its effect on STI susceptibility is much less explored. Using a mouse model of genital herpes simplex virus type 2 (HSV-2) infection, we herein found that DMPA and LNG similarly reduced genital expression of the desmosomal cadherin desmoglein-1α (DSG1α), enhanced access of inflammatory cells to genital tissue by increasing mucosal epithelial permeability, and increased susceptibility to viral infection. Additional studies with uninfected mice revealed that DMPA-mediated increases in mucosal permeability promoted tissue inflammation by facilitating endogenous vaginal microbiota invasion. Conversely, concomitant treatment of mice with DMPA and intravaginal estrogen restored mucosal barrier function and prevented HSV-2 infection. Evaluating ectocervical biopsy tissue from women before and 1 month after initiating DMPA remarkably revealed that inflammation and barrier protection were altered by treatment identically to changes seen in progestin-treated mice. Together, our work reveals DMPA and LNG diminish the genital mucosal barrier; a first-line defense against all STI, but may offer foundation for new contraceptive strategies less compromising of barrier protection.

Mucosal Immunology (2016) 9, 1571–1583; doi:10.1038/mi.2016.22

https://www.nature.com/mi/journal/v9/n6/full/mi201622a.html

Md. Rodolfo D. Vicetti Miguel, Ex-Miembro del GII

Md. Nirk E. Quispe Calla, Past President del GII