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

  title={Cataloguing of Potential HIV Susceptibility Factors during the Menstrual Cycle of Pig-Tailed Macaques by Using a Systems Biology Approach},
  author={Sundaram A Vishwanathan and Adam D. Burgener and Steven E. Bosinger and Gregory K. Tharp and Patricia C. Guenthner and Nirav B. Patel and Kenzie D. M. Birse and Debra L. Hanson and Garrett Westmacott and Tara Randolph Henning and Jessica A. Radzio and Jos{\'e} Gerardo Garc{\'i}a-Lerma and T. Blake Ball and Janet M Mcnicholl and Ellen N. Kersh},
  journal={Journal of Virology},
  pages={9167 - 9177}
ABSTRACT 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… 

Molecular Signatures of Immune Activation and Epithelial Barrier Remodeling Are Enhanced during the Luteal Phase of the Menstrual Cycle: Implications for HIV Susceptibility

A strong association between proteins involved in tissue remodeling and leukocyte infiltration with the luteal phase is indicated, which may represent potential hormone-associated mechanisms of increased susceptibility to HIV.

Factors associated with HIV susceptibility in the female genital tract

Women in HIV-serodiscordant relationships have a unique cervicovaginal environment, and that this may be associated with an altered susceptibility to HIV infection, according to Observational and experimental studies indicate that use of the injectable progestin-based contraceptive depot medroxyprogesterone acetate (DMPA) is associated with increased risk of HIV.

Progestin‐based contraception regimens modulate expression of putative HIV risk factors in the vaginal epithelium of pig‐tailed Macaques

It is hypothesized that progestin‐based contraception, especially depot medroxyprogesterone acetate (DMPA), would, in a similar way, affect mucosal immune factors that influence HIV acquisition risk.

Increases in Endogenous or Exogenous Progestins Promote Virus-Target Cell Interactions within the Non-human Primate Female Reproductive Tract

It is suggested that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progest in non-human primate models.

Role of Sex Hormones in Regulating Innate Immune Protection against HIV in the Human Female Reproductive Tract

The goal of this review is to summarize the multiple levels of protection against HIV infection in the FRT and thereby providing a foundation for the design of vaccines for protection against sexually-transmitted infections (STI) including HIV.

Hormonal influence on HIV‐1 transmission in the female genital tract: New insights from systems biology

This review focuses on the current understanding of the acute events that occur in the FGT following HIV‐1 exposure with a particular focus on the effect of endogenous and exogenous sex hormones on HIV‐ 1 susceptibility.

Type I IFNs in the female reproductive tract: The first line of defense in an ever‐changing battleground

What is currently known about type I IFN‐mediated immunity in the FRT in human, primate, and murine models is reviewed and their importance with respect to three highly relevant FRT infections: HIV, Zika, and Chlamydia is explored.

Sex and gender differences in HIV-1 infection.

It is discussed how a better understanding of the underlying mechanisms could improve preventive and therapeutic strategies and how oestrogen receptor signalling could represent an important mediator of sex differences in HIV-1 reservoir size and may represent a potential therapeutic target.

Nonhuman primate models for the evaluation of HIV-1 preventive vaccine strategies: model parameter considerations and consequences

Key model parameter options are discussed and new insights into basic disease mechanisms and improved models for better preclinical evaluation of interventions to prevent HIV transmission are promised.

Characterization of the Genital Mucosa Immune Profile to Distinguish Phases of the Menstrual Cycle: Implications for HIV Susceptibility

The follicular phase of the menstrual cycle was associated with elevated level of cervical CCL2 and retention of resident memory CD4+ T cells and the impact of endogenous sexual hormones on the mucosal immune response was compared.



High Susceptibility to Repeated, Low-Dose, Vaginal SHIV Exposure Late in the Luteal Phase of the Menstrual Cycle of Pigtail Macaques

The data support the findings of higher susceptibility to HIV in women during progesterone-dominated periods including pregnancy and contraceptive use and suggest that susceptibility to vaginal SHIV infection is significantly elevated in the second half of the menstrual cycle when progester one levels are high and when local immunity may be low.

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

The entire 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 cellmediated and innate immune systems throughout theFRT.

Productive HIV-1 Infection of Human Cervical Tissue Ex Vivo is Associated with the Secretory Phase of the Menstrual Cycle

The results support the epidemiological observation that sexual HIV-1 transmission from males to women as well as from women to men is more efficient during their secretory phase of the menstrual cycle.

Increased susceptibility to vaginal simian/human immunodeficiency virus transmission in pig-tailed macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis.

A macaque model for studies of high-risk HIV transmission and prevention is established and a biological link between these nonulcerative STIs and the risk of SHIV infection is demonstrated, supporting epidemiological associations of HIV and STIs.

A Systems Biology Examination of the Human Female Genital Tract Shows Compartmentalization of Immune Factor Expression

Immune factor abundance is heterogeneous throughout the female genital tract and shows unique immune microenvironments for HIV based on the exposure site, which may have important implications for early events in HIV transmission and site-specific susceptibility to HIV in the FGT.

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

Pregnancy and other high progesterone states may predispose women to HIV-1 acquisition, and CCR5 mRNA expression correlated with the cell surface marker expression from blood and tissue.

Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection

Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI, providing evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses.

MCP-1-MCP-3–Eotaxin gene cluster influences HIV-1 transmission

Although the extensive linkage disequilibrium precludes positive identification of the causal variant, the results suggest that genetic variation in the H7 region influences susceptibility to HIV-1 infection.

Physiologic doses of depot-medroxyprogesterone acetate do not increase acute plasma simian HIV viremia or mucosal virus shedding in pigtail macaques

Little or no effect of DMPA is found on plasma viremia and mucosal virus shedding during acute infection of pigtail macaques and these results do not support a role ofDMPA in increasing mucosal HIV shedding.

Comprehensive proteomic study identifies serpin and cystatin antiproteases as novel correlates of HIV-1 resistance in the cervicovaginal mucosa of female sex workers.

A large clinical study using the tools of systems biology to fully characterize the cervicovaginal mucosa proteome in HIV-1-resistant women identifies mucosal serpins and cystatins as novel correlates of HIV- 1-resistance.