The Effect of Progesterone Levels and Pregnancy on HIV-1 Coreceptor Expression

Sheffield, Jeanne S.; Wendel, George D.; McIntire, Donald D.; Norgard, Michael V.

doi:10.1177/1933719108325510

Cited by 61 publications

(50 citation statements)

References 66 publications

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Section: No Significant Differences In Vaginal Immune Cells Between Fmentioning

confidence: 99%

“…45 Although this study accounts for a range of endogenous hormonal states, it is likely that the inflammatory state of the genital tract and other covariates differed significantly among cohorts. 45 No significant differences in the antimicrobial activity of the CVL The secretion of cervical mucus is significantly influenced by endogenous reproductive hormones, with cervical mucus volume peaking with surges in preovulatory serum E2. [46][47][48] The biologic rationale for differences in antimicrobial activity of the CVL is based on data from small cohorts showing that secreted cytokines, chemokines, and other cationic antimicrobial polypeptides in the vagina have significant alterations in concentrations based on the phase of the menstrual cycle with immune factors such as IL-6, IL-1b, IL-1RA, and MIP-1b being significantly higher in the FOL phase versus the LUT phase, 19,27 while IL-1a and b-defensin were significantly elevated in the LUT phase.…”

Section: No Significant Differences In Vaginal Immune Cells Between Fmentioning

confidence: 99%

“…44 In a small cross-sectional study, including men, postmenopausal, and pregnant and nonpregnant premenopausal women, serum P4 levels were significantly associated with CCR5 expression on peripheral blood mononuclear cells (PBMCs). 45 Vaginal tissue biopsies were obtained from a subset of the pregnant women (n = 12), including three women in active labor. Pregnant and laboring women had significantly higher proportions of vaginal CD3…”

Section: No Significant Differences In Vaginal Immune Cells Between Fmentioning

confidence: 99%

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Comparison of Follicular and Luteal Phase Mucosal Markers of HIV Susceptibility in Healthy Women

Thurman

Chandra

Yousefieh

et al. 2016

AIDS Research and Human Retroviruses

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The purpose of this study was to evaluate differences in vaginal immune cell populations, vaginal tissue gene expression, antimicrobial activity of the cervicovaginal (CV) lavage (CVL), vaginal flora, and p24 antigen production from CV tissues after ex vivo human immunodeficiency virus (HIV) infection between follicular (FOL) and luteal (LUT) phases of the menstrual cycle. CV tissue biopsies, CV secretions, and blood samples were obtained as part of two longitudinal clinical trials of healthy women (CONRAD D11-119 and A12-124 studies). Participants (n = 39) were HIV-seronegative women not using exogenous hormone supplementation, with normal menstrual cycles, who were screened to exclude sexually transmitted and reproductive tract infections. Serum levels of estradiol and progesterone were significantly higher in the LUT versus the FOL phase of the menstrual cycle. Controlling for race, reported contraceptive use/sexual practices, and clinical trial, we found no differences in vaginal tissue immune cell populations and activation status, transcriptomes, inhibition of HIV, herpes simplex virus type 2 and Escherichia coli by the CVL, vaginal pH or Nugent score, or production of p24 antigen after ex vivo infection by HIV-1 BaL between CV samples obtained in the FOL phase versus the LUT phase of the menstrual cycle. There were no significant correlations between serum estradiol and progesterone levels and CV endpoints. The hypothesis that the LUT phase of the menstrual cycle represents a more vulnerable stage for mucosal infection with HIV was not supported by data from samples obtained from the lower genital tract (ectocervix and vagina) from these two clinical trials.

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Section: No Significant Differences In Vaginal Immune Cells Between Fmentioning

confidence: 99%

Section: No Significant Differences In Vaginal Immune Cells Between Fmentioning

confidence: 99%

Section: No Significant Differences In Vaginal Immune Cells Between Fmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of Follicular and Luteal Phase Mucosal Markers of HIV Susceptibility in Healthy Women

Thurman

Chandra

Yousefieh

et al. 2016

AIDS Research and Human Retroviruses

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“…39 Furthermore, women in various progesterone-dominant states have been found to have increased expression of cervical and vaginal lymphocytes expressing CCR5. [39][40][41] Interestingly, they have also been shown to have increased susceptibility to acquire HIV-1. [42][43][44][45] CCR5 is known to be expressed by activated lymphocytes.…”

Section: Figmentioning

confidence: 99%

Depot Medroxyprogesterone Acetate Increases Immune Cell Numbers and Activation Markers in Human Vaginal Mucosal Tissues

Chandra

Thurman

Anderson

et al. 2013

AIDS Research and Human Retroviruses

102

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The relationship between exogenous contraceptive hormones and permissiveness of the female genital tract to human immunodeficiency virus type 1 (HIV-1) is the subject of renewed debate. To better characterize the effect of depot medroxyprogesterone acetate (DMPA) on HIV-1 cellular targets and epithelial integrity in the vagina, we compared leukocyte populations, markers of activation and proliferation, and the density of intercellular junctional proteins in the vaginal epithelium of women during the follicular and luteal phases of the menstrual cycle and approximately 12 weeks after receiving a DMPA injection. This prospective cohort study involved 15 healthy women. Vaginal biopsies were obtained in the follicular and luteal phases of the menstrual cycle, and approximately 12 weeks following a 150-mg intramuscular injection of DMPA. Leukocyte populations, activation phenotype, and epithelial tight junction and adherens proteins were evaluated by immunohistochemistry. After receiving DMPA, the numbers of CD45, CD3, CD8, CD68, HLA-DR, and CCR5 bearing immune cells were significantly ( p < 0.05) increased in vaginal tissues, compared to the follicular and/or luteal phases of untreated cycles. There were no significant differences in immune cell populations between the follicular and luteal phases of the control cycle. There were also no statistically significant differences in epithelial thickness and density of epithelial tight junction and adherens proteins among the follicular, luteal, and post-DMPA treatment sampling points. In this pilot study, vaginal immune cell populations were significantly altered by exogenous progesterone, resulting in increased numbers of T cells, macrophages, and HLA-DR-and CCR5-positive cells.

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“…With menstrual cycling patterns similar to those in humans, and the previously reported success in infecting the animals at low virus doses without hormonal intervention, pig-tailed macaques have become unique animal models for HIV studies; their importance is especially underscored in testing menstrual phase-dependent susceptibility to HIV, considering the difficulty in conducting such studies with normally cycling women. The luteal phase is characterized by higher levels of progesterone, which have been associated with depressed immune responses, vaginal epithelial thinning (less in humans than in macaques), and other factors that increase risk of HIV-1 acquisition (7)(8)(9). Although this has not been directly tested, there are public health implications to the possibility that women on progestin-based contraception might exhibit a lack of immune responses akin to those seen in the luteal phase, thus increasing risk of HIV-1 acquisition.…”

mentioning

confidence: 99%

Cataloguing of Potential HIV Susceptibility Factors during the Menstrual Cycle of Pig-Tailed Macaques by Using a Systems Biology Approach

Vishwanathan

Burgener

Bosinger

et al. 2015

J Virol

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Our earlier studies with pig-tailed macaques demonstrated various simian-human immunodeficiency virus (SHIV) susceptibilities during the menstrual cycle, likely caused by cyclic variations in immune responses in the female genital tract. There is concern that high-dose, long-lasting, injectable progestin-based contraception could mimic the high-progesterone luteal phase and predispose women to human immunodeficiency type 1 (HIV-1) acquisition and transmission. In this study, we adopted a systems biology approach employing proteomics (tandem mass spectrometry), transcriptomics (RNA microarray hybridization), and other specific protein assays (enzyme-linked immunosorbent assays and multiplex chemokine and cytokine measurements) to characterize the effects of hormonal changes on the expression of innate factors and secreted proteins in the macaque vagina. Several antiviral factors and pathways (including acute-phase response signaling and complement system) were overexpressed in the follicular phase. Conversely, during the luteal phase there were factors overexpressed (including moesins, syndecans, and integrins, among others) that could play direct or indirect roles in enhancing HIV-1 infection. Thus, our study showed that specific pathways and proteins or genes might work in tandem to regulate innate immunity, thus fostering further investigation and future design of approaches to help counter HIV-1 acquisition in the female genital tract. IMPORTANCEHIV infection in women is poorly understood. High levels of the hormone progesterone may make women more vulnerable to infection. This could be the case during the menstrual cycle, when using hormone-based birth control, or during pregnancy. The biological basis for increased HIV vulnerability is not known. We used an animal model with high risk for infection during periods of high progesterone. Genital secretions and tissues during the menstrual cycle were studied. Our goal was to identify biological factors upregulated at high progesterone levels, and we indeed show an upregulation of genes and proteins which enhance the ability of HIV to infect when progesterone is high. In contrast, during low-progesterone periods, we found more HIV inhibitory factors. This study contributes to our understanding of mechanisms that may regulate HIV infection in females under hormonal influences. Such knowledge is needed for the development of novel prevention strategies. F emale acquisition of human immunodeficiency virus type 1 (HIV-1) is not an efficient process, and transmission events are estimated to occur at frequencies of 1/100 to 1/1,000 exposures (1; reviewed in reference 2). Despite this, the heterosexual route is the predominant mode of HIV-1 transmission worldwide (3), and the development of strategies to reduce male-to-female vaginal transmission rates remains a priority. Animal studies have demonstrated that the time between vaginal exposure and virus detection in draining lymph nodes is as little as 1 to 3 days. There is a small window of early protection whe...

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The Effect of Progesterone Levels and Pregnancy on HIV-1 Coreceptor Expression

Cited by 61 publications

References 66 publications

Comparison of Follicular and Luteal Phase Mucosal Markers of HIV Susceptibility in Healthy Women

Comparison of Follicular and Luteal Phase Mucosal Markers of HIV Susceptibility in Healthy Women

Depot Medroxyprogesterone Acetate Increases Immune Cell Numbers and Activation Markers in Human Vaginal Mucosal Tissues

Cataloguing of Potential HIV Susceptibility Factors during the Menstrual Cycle of Pig-Tailed Macaques by Using a Systems Biology Approach

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