Ferreira Victor H, Dizzell Sara, Nazli Aisha, Kafka Jessica K, Mueller Kristen, Nguyen Philip V, Tremblay Michel J, Cochrane Alan, Kaushic Charu
Deptartment of Pathology and Molecular Medicine McMaster Immunology Research Centre, McMaster University, Hamilton.
Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec City, Canada.
J Infect Dis. 2015 Jun 1;211(11):1745-56. doi: 10.1093/infdis/jiu832. Epub 2014 Dec 23.
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.
尽管临床和实验证据表明，女性性激素和激素避孕药可调节对1型人类免疫缺陷病毒（HIV-1）感染的易感性，但其潜在机制仍不清楚。生殖上皮细胞（GECs）是性传播过程中最先接触HIV的细胞，它们与HIV的相互作用可能决定接触的结果。这是第一份报告指出，在激素避孕药醋酸甲羟孕酮（MPA）和孕酮存在的情况下，GECs对HIV的摄取显著增加，且摄取主要通过内吞作用发生。未检测到有生产性感染，但内吞的病毒被释放到顶端和基底外侧区室。在MPA存在的情况下，观察到明显更高的病毒转胞吞作用。在GEC和T细胞共培养中，在MPA存在的情况下观察到T细胞中最大程度的病毒复制，MPA还广泛上调了GECs趋化因子的产生。这些结果表明，MPA可能在调节对HIV的易感性方面发挥重要作用。
