Obstetric outcomes of human herpes virus-2 infection among pregnant women in Benin, Nigeria

Kalu, Eziyi Iche; Ojide, Chiedozie Kingsley; Chuku, Abali; Chukwuonye, Innocent Ijezie; Agwu, F E; Nwadike, Victor; Korie, Francis Chukwuma; Okafor, Godwin Oguejiofor Chukwuebuka

doi:10.4103/1119-3077.154210

Cited by 12 publications

(9 citation statements)

References 17 publications

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“…Increasingly, infectious and inflammatory diseases are being attributed to combinations of different infectious kingdoms (21), including pregnancy complications like preterm birth (61). Furthermore, the impact viruses may have on pregnancy outcomes are beginning to be appreciated (31, 62, 63). The current study set out to test the impact a polymicrobial infection could have on human fetal membrane innate immune responses and the mechanisms involved.…”

Section: Discussionmentioning

confidence: 99%

“…While not all women with a viral infection during pregnancy will have complications, some viruses that are detected in the amniotic fluid or gestational tissues have been linked to an increased risk for chorioamnionitis and preterm birth. These include adenovirus, and herpes viruses, such as cytomegalovirus (CMV), Epstein-Barr virus and herpes simplex virus (HSV) (22–31). If a virus, that can infect the placenta and FMs, increases a woman’s risk for preterm birth by altering local responses to bacterial components, then the mechanisms likely involve modulation of innate immune receptors and their regulators.…”

Section: Introductionmentioning

confidence: 99%

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Viral Infection Sensitizes Human Fetal Membranes to Bacterial Lipopolysaccharide by MERTK Inhibition and Inflammasome Activation

Cross

Potter

Aldo

et al. 2017

The Journal of Immunology

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Chorioamnionitis, premature rupture of fetal membranes (FM), and subsequent preterm birth are associated with local infection and inflammation, particularly interleukin 1 beta (IL-1β) production. While bacterial infections are commonly identified, other microorganisms may play a role in the pathogenesis. Since viral pandemics, such as influenza, Ebola and Zika are becoming more common, and pregnant women are at increased risk of associated complications, this study evaluated the impact viral infection had on human FM innate immune responses. This study shows that a herpes viral infection of FMs sensitizes the tissue to low levels of bacterial lipopolysaccharide (LPS), giving rise to an exaggerated IL-1β response. Using an ex vivo human FM explant system and an in vivo mouse model of pregnancy, we report that the mechanism by which this aggravated inflammation arises is through the inhibition of the TAM receptor, MERTK, and activation of the inflammasome. The TAM receptor ligand, growth arrest specific 6 (GAS6), re-establishes the normal FM response to LPS by restoring and augmenting TAM receptor and ligand expression, and by preventing the exacerbated IL-1β processing and secretion. These findings indicate a novel mechanism by which viruses alter normal FM immune responses to bacteria, potentially giving rise to adverse pregnancy outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Viral Infection Sensitizes Human Fetal Membranes to Bacterial Lipopolysaccharide by MERTK Inhibition and Inflammasome Activation

Cross

Potter

Aldo

et al. 2017

The Journal of Immunology

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“…Indeed, genital herpes DNA was demonstrated in both amniotic fluid and placental tissue of preterm deliveries [12, 14]. Similarly, women who recently seroconverted for HSV-2 had an increased risk of preterm delivery and babies with low birth weight [15]. …”

Section: Introductionmentioning

confidence: 99%

Effect of suppressive acyclovir administered to HSV-2 positive mothers from week 28 to 36 weeks of pregnancy on adverse obstetric outcomes: a double-blind randomised placebo-controlled trial

et al. 2017

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Background: Acyclovir (ACV) given to HSV-2 positive women after 36 weeks reduces adverse outcomes but its benefit at lower gestation was undocumented. We determined the effect of oral acyclovir administered from 28 to 36 weeks on premature rupture of membranes (PROM) primarily and preterm delivery risk.Methods: This was a randomized, double-blind placebo-controlled trial among 200 HSV-2 positive pregnant women at 28 weeks of gestation at Mulago Hospital, Uganda. Participants were assigned randomly (1:1) to take either acyclovir 400 mg orally twice daily (intervention) or placebo (control) from 28 to 36 weeks. Both arms received acyclovir after 36 weeks until delivery. Development of Pre-PROM by 36 weeks and preterm delivery were outcomes.

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“…Since we observed histopathology that indicated deficiencies in maternal blood flow and exchange capacity in infected animals, and because HSV-2 infection in human pregnancies is linked to several adverse outcomes including IUGR and low birth weight [14,16], we next investigated the effect of primary HSV-2 infection on fetal weight and development in our animal model. At the time of sacrifice, placental tissues and fetuses were dissected and weighed separately.…”

Section: Hsv-2 Infection Of Maternal and Fetal Placental Tissues Correlates With Histopathologymentioning

confidence: 99%

“…Among women seropositive for HSV-2, approximately 75% will have at least one recurrence of active viral infection before the third trimester [12,13] and 14% will have prodromal symptoms or clinical recurrence at the time of delivery [13]. Compared with uninfected pregnancies, intrauterine HSV-2 infection is linked to numerous adverse pregnancy outcomes including spontaneous abortion [14][15][16], stillbirth [9,14,17], intrauterine growth restriction (IUGR) [14,18,19], low birth weight [16,18], and preterm birth [7,14,16,18,20].…”

Section: Introductionmentioning

confidence: 99%

Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model

Felker

Nguyen

Kaushic

2021

Viruses

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Herpes simplex virus type 2 (HSV-2) infection affects 24 million births annually and is associated with adverse pregnancy outcomes, including neonatal herpes; however, the mechanisms underlying in utero transmission of HSV-2 are largely unknown. We examined the effects of primary HSV-2 infection during early pregnancy on gestational outcomes in a novel, clinically relevant mouse model. Pregnant C57BL/6 mice were infected intravaginally with 102–105 pfu/mL HSV-2 on gestation day (gd) 4.5. Controls were infected, nonpregnant, diestrus-staged mice and pregnant, uninfected mice. Compared to nonpregnant mice, pregnant mice were 100-fold more susceptible to HSV-2 infection. Three days post-inoculation (gd7.5), viral DNA was present in implantation sites, but pregnancy outcomes were largely unaffected by infection. Eight days post-inoculation (gd12.5), HSV-2 DNA persisted in placental tissues, resulting in inflammation and hemorrhage. Fetal and placental weights were reduced and fetal loss was observed with high viral doses. HSV-2 DNA and increased expression of pro-inflammatory mediators were detected in fetal tissues at gd12.5, signifying viral transmission and fetal infection, even with low viral doses. This mouse model shows a dose-dependent effect of primary HSV-2 infection on pregnancy outcomes and suggests that fetal loss may occur due to placental inflammation, thus providing valuable insight into in utero transmission of HSV-2.

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Obstetric outcomes of human herpes virus-2 infection among pregnant women in Benin, Nigeria

Abstract: First episode HSV-2 infection among pregnant women in Benin, Nigeria is associated with an increased risk of occurrence of spontaneous abortion, LBW delivery, stillbirths, and preterm delivery.

Cited by 12 publications

References 17 publications

Viral Infection Sensitizes Human Fetal Membranes to Bacterial Lipopolysaccharide by MERTK Inhibition and Inflammasome Activation

Viral Infection Sensitizes Human Fetal Membranes to Bacterial Lipopolysaccharide by MERTK Inhibition and Inflammasome Activation

Effect of suppressive acyclovir administered to HSV-2 positive mothers from week 28 to 36 weeks of pregnancy on adverse obstetric outcomes: a double-blind randomised placebo-controlled trial

Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model

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