1. Medroxyprogesterone Acetate Regulates HIV-1 Uptake and Transcytosis but Not Replication in Primary Genital Epithelial Cells, Resulting in Enhanced T-Cell Infection.
- Author
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Ferreira VH, Dizzell S, Nazli A, Kafka JK, Mueller K, Nguyen PV, Tremblay MJ, Cochrane A, and Kaushic C
- Subjects
- Cells, Cultured, Contraceptive Agents, Female pharmacology, Cytokines metabolism, Endocytosis, Female, Humans, Progesterone pharmacology, Up-Regulation, Uterus cytology, Epithelial Cells virology, HIV Infections virology, HIV-1 drug effects, Medroxyprogesterone Acetate pharmacology, T-Lymphocytes virology, Virus Internalization drug effects, Virus Replication drug effects
- Abstract
Although clinical and experimental evidence indicates that female sex hormones and hormonal contraceptives regulate susceptibility to human immunodeficiency virus type 1 (HIV-1) infection, the underlying mechanism remains unknown. Genital epithelial cells (GECs) are the first cells to encounter HIV during sexual transmission and their interaction with HIV may determine the outcome of exposure. This is the first report that HIV uptake by GECs increased significantly in the presence of the hormonal contraceptive medroxyprogesterone acetate (MPA) and progesterone and that uptake occurred primarily via endocytosis. No productive infection was detected, but endocytosed virus was released into apical and basolateral compartments. Significantly higher viral transcytosis was observed in the presence of MPA. In GEC and T-cell cocultures, maximum viral replication in T cells was observed in the presence of MPA, which also broadly upregulated chemokine production by GECs. These results suggest that MPA may play a significant role in regulating susceptibility to HIV., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2015
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