Interactions between HIV-1 and Mucosal Cells in the Female Reproductive Tract

While vitamin D insufficiency is known to impact a multitude of health outcomes, including HIV-1, little is known about the role of vitamin D-mediated immune regulation in the female reproductive tract (FRT). We performed a pilot clinical study of 20 women with circulating 25(OH)D levels <62.5 nmol/L. Participants were randomized into either weekly or daily high-dose oral vitamin D supplementation groups. In addition to serum vitamin D levels, genital mucosal endpoints, including soluble mediators, immune cell populations, gene expression, and ex vivo HIV-1 infection, were assessed. While systemic vitamin D levels showed a significant increase following supplementation, these changes translated into modest effects on the cervicovaginal factors studied. Paradoxically, post-supplementation vitamin D levels were decreased in cervicovaginal fluids. Given the strong correlation between vitamin D status and HIV-1 infection and the widespread nature of vitamin D deficiency, further understanding of the role of vitamin D immunoregulation in the female reproductive tract is important.

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HIV-1 Infection in the Female Reproductive Tract: Role of Interactions between HIV-1 and Genital Epithelial Cells

American Journal of Reproductive Immunology ◽

10.1111/j.1600-0897.2010.00965.x ◽

2011 ◽

Vol 65 (3) ◽

pp. 253-260 ◽

Cited By ~ 40

Author(s):

Charu Kaushic

Keyword(s):

Epithelial Cells ◽

Reproductive Tract ◽

Female Reproductive Tract ◽

Hiv 1

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Pathogen Recognition in the Human Female Reproductive Tract: Expression of Intracellular Cytosolic Sensors NOD1, NOD2, RIG-1, and MDA5 and response to HIV-1 andNeisseria gonorrhea

American Journal of Reproductive Immunology ◽

10.1111/aji.12019 ◽

2012 ◽

Vol 69 (1) ◽

pp. 41-51 ◽

Cited By ~ 24

Author(s):

Mimi Ghosh ◽

Zheng Shen ◽

John V. Fahey ◽

Sarah G. Crist ◽

Mickey Patel ◽

...

Keyword(s):

Reproductive Tract ◽

Female Reproductive Tract ◽

Human Female ◽

Pathogen Recognition ◽

Hiv 1

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Mucosal Immunity in HIV/SIV Infection: T Cells, B Cells and Beyond

Current Immunology Reviews ◽

10.2174/1573395514666180528081204 ◽

2019 ◽

Vol 15 (1) ◽

pp. 63-75 ◽

Cited By ~ 3

Author(s):

Barbara L. Shacklett

Keyword(s):

T Cells ◽

Mucosal Immunity ◽

Reproductive Tract ◽

Cell Types ◽

Female Reproductive Tract ◽

Multiparameter Flow Cytometry ◽

Mucosal Tissues ◽

New Information ◽

Innate Lymphocytes ◽

Hiv 1

As our understanding of mucosal immunity increases, it is becoming clear that the host response to HIV-1 is more complex and nuanced than originally believed. The mucosal landscape is populated with a variety of specialized cell types whose functions include combating infectious agents while preserving commensal microbiota, maintaining barrier integrity, and ensuring immune homeostasis. Advances in multiparameter flow cytometry, gene expression analysis and bioinformatics have allowed more detailed characterization of these cell types and their roles in host defense than was previously possible. This review provides an overview of existing literature on immunity to HIV-1 and SIVmac in mucosal tissues of the female reproductive tract and the gastrointestinal tract, focusing on major effector cell populations and briefly summarizing new information on tissue-resident memory T cells, Treg, Th17, Th22 and innate lymphocytes (ILC), subsets that have been studied primarily in the gastrointestinal mucosa.

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Characterization of the Influence of Semen-Derived Enhancer of Virus Infection on the Interaction of HIV-1 with Female Reproductive Tract Tissues

Journal of Virology ◽

10.1128/jvi.00309-15 ◽

2015 ◽

Vol 89 (10) ◽

pp. 5569-5580 ◽

Cited By ~ 17

Author(s):

Shannon A. Allen ◽

Ann M. Carias ◽

Meegan R. Anderson ◽

Eneniziaogochukwu A. Okocha ◽

Lorie Benning ◽

...

Keyword(s):

Cell Culture ◽

Virus Infection ◽

Reproductive Tract ◽

Sexual Transmission ◽

Female Reproductive Tract ◽

Productive Infection ◽

Target Cells ◽

Mucosal Transmission ◽

Epithelial Barriers ◽

Hiv 1

ABSTRACTThe majority of human immunodeficiency virus type 1 (HIV-1) transmission events occur in women when semen harboring infectious virus is deposited onto the mucosal barriers of the vaginal, ectocervical, and endocervical epithelia. Seminal factors such as semen-derived enhancer of virus infection (SEVI) fibrils were previously shown to greatly enhance the infectivity of HIV-1 in cell culture systems. However, when SEVI is intravaginally applied to living animals, there is no effect on vaginal transmission. To define how SEVI might function in the context of sexual transmission, we applied HIV-1 and SEVI to intact human and rhesus macaque reproductive tract tissues to determine how it influences virus interactions with these barriers. We show that SEVI binds HIV-1 and sequesters most virions to the luminal surface of the stratified squamous epithelium, significantly reducing the number of virions that penetrated the tissue. In the simple columnar epithelium, SEVI was no longer fibrillar in structure and was detached from virions but allowed significantly deeper epithelial virus penetration. These observations reveal that the action of SEVI in intact tissues is very different in the anatomical context of sexual transmission and begin to explain the lack of stimulation of infection observed in the highly relevant mucosal transmission model.IMPORTANCEThe most common mode of HIV-1 transmission in women occurs via genital exposure to the semen of HIV-infected men. A productive infection requires the virus to penetrate female reproductive tract epithelial barriers to infect underlying target cells. Certain factors identified within semen, termed semen-derived enhancers of virus infection (SEVI), have been shown to significantly enhance HIV-1 infectivity in cell culture. However, when applied to the genital tracts of living female macaques, SEVI did not enhance virus transmission. Here we show that SEVI functions very differently in the context of intact mucosal tissues. SEVI decreases HIV-1 penetration of squamous epithelial barriers in humans and macaques. At the mucus-coated columnar epithelial barrier, the HIV-1/SEVI interaction is disrupted. These observations suggest that SEVI may not play a significant stimulatory role in the efficiency of male-to-female sexual transmission of HIV.

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