A new strategy to understand how HIV infects women: identification of a window of vulnerability during the menstrual cycle

摘要

Although 85% of new HIV cases are due to sexual transmission from men to women, little attention is being paid to the immune system in the female reproductive tract (FRT), and to how it meets the conflicting challenges of protecting from pathogens and permitting procreation. As a new approach we have tried to envision how HIV evades FRT mucosal immune protection and have been led to the unexpected conclusion that in a normal menstrual cycle, there is a window of vulnerability (7-10 days following ovulation) in which the potential for viral infectivity in the FRT is enhanced. During that period, aspects of the innate, humoral, and cell-mediated immune systems are suppressed by sex hormones to optimize conditions for procreation. Suppression occurs in the upper (Fallopian tubes, uterus, endocervix) and lower (ectocervix and vagina) FRT, and coincides with the recruitment of potentially infectable cells and upregulation of coreceptors essential for viral uptake. Implications of these findings are that theentire FRT is a potential target for HIV infection, immune cells and antibodies in blood are not surrogate markers for immune protection in the FRT, and immune protection against HIV will require an understanding of the hormone-induced regulation of humoral, cell-mediated, and innate immune systems throughout the FRT#