Role of Semen in HIV‐1 Transmission: Inhibitor or facilitator?

Doncel, Gustavo F.; Joseph, Theresa; Thurman, Andrea Ries

doi:10.1111/j.1600-0897.2010.00931.x

Cited by 62 publications

(43 citation statements)

References 77 publications

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“…Semen is more than a mere carrier of HIV-1, since it contains many biological factors that may facilitate or inhibit HIV-1 transmission 41 . For instance, semen neutralizes the acidic cervical mucus increasing HIV-1 diffusion 42 otherwise trapped in mucus 43 .…”

Section: Semen Affects Hiv Acquisitionmentioning

confidence: 99%

HIV‐1 Vaginal Transmission: Cell‐Free or Cell‐Associated Virus?

Barreto-de-Souza

Arakelyan

Margolis

et al. 2014

American J Rep Immunol

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The vast majority of new HIV infections in male-to-female transmission occurs through semen, where HIV-1 is present in two different forms: as free and as cell-associated virus. In the female lower genital tract, semen mixes with female genital secretions that contain various factors, some of which facilitate or inhibit HIV-1 transmission. Next, HIV-1 crosses the genital epithelia, reaches the regional lymph nodes, and disseminates through the female host. Cervico-vaginal mucosa contains multiple barriers, resulting in a low probability of vaginal transmission. However, in some cases HIV-1 is able to break these barriers. Although the exact mechanisms of how these barriers function remain unclear, their levels of efficiency against cell-free and cell-associated HIV-1 are different, and both cell-free and cell-associated virions seem to use different strategies to overcome these barriers. Understanding the basic mechanisms of HIV-1 vaginal transmission is required for the development of new antiviral strategies to contain HIV-1 epidemics.

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Section: Semen Affects Hiv Acquisitionmentioning

confidence: 99%

HIV‐1 Vaginal Transmission: Cell‐Free or Cell‐Associated Virus?

Barreto-de-Souza

Arakelyan

Margolis

et al. 2014

American J Rep Immunol

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“…Previous in vitro studies have shown that human semen enhances HIV-1 infectivity independent of tropism (1)(2)(3)(4). Some investigations suggest a proinflammatory role when semen is introduced to the genital tract such that it alters the activation state of potential target cells and neutralizes the native acidic pH (5). Still, findings presented elsewhere suggest a target cell-specific protective effect of semen (6)(7)(8)(9).…”

mentioning

confidence: 91%

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

Allen

Carias

Anderson

et al. 2015

J Virol

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The 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.

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“…The sites of inflammation are enriched with HIV target immune cells and may have breaches in the mucosal epithelial barrier, both of which facilitate HIV acquisition [4]. Seminal plasma (SP) is the main vector for HIV in sexual transmission, but SP is not only a carrier for HIV [5,6]. In vitro studies have shown that SP may both inhibit and facilitate HIV infection.…”

Section: Introductionmentioning

confidence: 99%

Seminal Plasma Induces Prostaglandin-Endoperoxide Synthase (PTGS) 2 Expression in Immortalized Human Vaginal Cells: Involvement of Semen Prostaglandin E2 in PTGS2 Upregulation1

Joseph

Zalenskaya

Sawyer

et al. 2013

Biology of Reproduction

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Inflammation of the cervicovaginal mucosa is considered a risk factor for HIV infection in heterosexual transmission. In this context, seminal plasma (SP) may play an important role that is not limited to being the main carrier for the virions. It is known that SP induces an inflammatory reaction in the cervix called postcoital leukocytic reaction, which has been associated with promotion of fertility. The mechanisms by which SP triggers this reaction, however, have not been clearly established. Previously we reported the expression of prostaglandin-endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase 2 (COX-2), in human vaginal cells in response to toll-like receptor (TLR) ligands and other proinflammatory stimuli. In this study, we demonstrate that SP induces transcriptional and translational increase of COX-2 expression in human vaginal cells and cervicovaginal tissue explants. Furthermore, SP potentiates vaginal PTGS2 expression induced by other proinflammatory stimulants, such as TLR ligands and a vaginal mucosal irritant (nonoxynol-9) in a synergistic manner. SP-induced PTGS2 expression is mediated by intracellular signaling pathways involving MAPKs and NF-κB. Using fractionation and functional analysis, seminal prostaglandin (PG)-E(2) was identified as a one of the major factors in PTGS2 induction. Given the critical role of this PG-producing enzyme in mucosal inflammatory processes, the finding that SP induces and potentiates the expression of PTGS2 in cervicovaginal cells and tissues has mechanistic implications for the role of SP in fertility-associated mucosal leukocytic reaction and its potential HIV infection-enhancing effect.

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Role of Semen in HIV‐1 Transmission: Inhibitor or facilitator?

Cited by 62 publications

References 77 publications

HIV‐1 Vaginal Transmission: Cell‐Free or Cell‐Associated Virus?

HIV‐1 Vaginal Transmission: Cell‐Free or Cell‐Associated Virus?

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

Seminal Plasma Induces Prostaglandin-Endoperoxide Synthase (PTGS) 2 Expression in Immortalized Human Vaginal Cells: Involvement of Semen Prostaglandin E2 in PTGS2 Upregulation1

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