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Medroxyprogesterone Acetate (MPA) Enhances HIV-1 Accumulation and Release in Primary Cervical Epithelial Cells by Inhibiting Lysosomal Activity.

Xiangxu Jia, Qiujia Shao, Ahsen R Chaudhry, Ballington L Kinlock, Michael G Izban, Hong-Ying Zhang, Fernando Villalta, James E K Hildreth, Bindong Liu

Pathogens (Basel, Switzerland)(2021)

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Abstract
Medroxyprogesterone acetate (MPA) is one of the most widely used contraceptives in the world. Epidemiologic studies have uncovered a possible link between the use of MPA and an increased risk of HIV-1 transmission. However, the understanding of the mechanism is still limited. Our previous publication demonstrated that the lysosomal activity in human vaginal epithelial cells attenuated the trafficking of viral particles during HIV-1 transcytosis. In this study, we show that treating human primary cervical epithelial cells with MPA led to a reduction in lysosomal activity. This reduction caused an increase in the intracellular HIV-1 accumulation and, consequently, an increase in viral release. Our study uncovers a novel mechanism by which MPA enhances HIV-1 release in primary cervical epithelial cells, thus providing vital information for HIV intervention and prevention.
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Key words
HIV-1,Medroxyprogesterone acetate,MPA,transmission,lysosome activity
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