Zika virus infection induces endoplasmic reticulum stress and apoptosis in placental trophoblasts

Muthuraj, Philma Glora; Sahoo, Prakash Kumar; Kraus, Madison; Bruett, Taylor; Annamalai, Arun S.; Pattnaik, Aryamav; Pattnaik, Asit K.; Byrareddy, Siddappa N.; Natarajan, Sathish Kumar

doi:10.1038/s41420-020-00379-8

Cited by 29 publications

(26 citation statements)

References 82 publications

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“…Interestingly, ZIKV infection is related to pro-inflammatory cytokine expression and apoptosis in placental explants, thus we propose that human placental explants can be used as a model for studying ZIKV infection in vitro (Ribeiro et al, 2018). Moreover, the mechanism of ZIKV-induced placental trophoblast apoptosis involves the activation of ER stress and JNK activation, and the inhibition of JNK dramatically prevents ZIKV-induced trophoblast apoptosis (Muthuraj et al, 2021).…”

Section: Zikv Regulation Of Apoptosismentioning

confidence: 94%

The Dual Regulation of Apoptosis by Flavivirus

et al. 2021

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Apoptosis is a form of programmed cell death, which maintains cellular homeostasis by eliminating pathogen-infected cells. It contains three signaling pathways: death receptor pathway, mitochondria-mediated pathway, and endoplasmic reticulum pathway. Its importance in host defenses is highlighted by the observation that many viruses evade, hinder or destroy apoptosis, thereby weakening the host’s immune response. Flaviviruses such as Dengue virus, Japanese encephalitis virus, and West Nile virus utilize various strategies to activate or inhibit cell apoptosis. This article reviews the research progress of apoptosis mechanism during flaviviruses infection, including flaviviruses proteins and subgenomic flaviviral RNA to regulate apoptosis by interacting with host proteins, as well as various signaling pathways involved in flaviviruses-induced apoptosis, which provides a scientific basis for understanding the pathogenesis of flaviviruses and helps in developing an effective antiviral therapy.

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Section: Zikv Regulation Of Apoptosismentioning

confidence: 94%

The Dual Regulation of Apoptosis by Flavivirus

et al. 2021

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“…Zika virus is known to cause apoptosis via sustained ER stress in the trophoblasts [30]. The principal findings of the present study are: (1) palmitoleate, an omega-7 monounsaturated fatty acid significantly reduces ZIKV infection-induced trophoblast apoptosis; (2) treatment of palmitoleate interferes with ZIKV replication in trophoblasts; (3) palmitoleate treatment after ZIKV infection in trophoblasts downregulates the activation of ER stress markers that occur due to viral protein overload; and (4) palmitate, a saturated fatty acid with similar carbon structure to palmitoleate augments cell death in ZIKV-infected trophoblasts.…”

Section: Discussionmentioning

confidence: 99%

“…We earlier demonstrated that ZIKV infection of trophoblasts induces an increase in the levels of C/EBP homologous protein (CHOP) mRNA and Spliced X box associated protein-1 (XBP1) mRNA, which are key markers of ER stress [30]. We assessed the activation of ER stress markers, namely CHOP mRNA expression and XBP1 gene splicing with palmitoleate or palmitate treatment to ZIKV-infected JEG-3 cells.…”

Section: Palmitoleate Protects Against Zikv-induced Endoplasmic Reticulum (Er) Stressmentioning

confidence: 99%

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Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis

et al. 2021

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Zika virus (ZIKV) infection in pregnancy is associated with the development of microcephaly, intrauterine growth restriction, and ocular damage in the fetus. ZIKV infection of the placenta plays a crucial role in the vertical transmission from the maternal circulation to the fetus. Our previous study suggested that ZIKV induces endoplasmic reticulum (ER) stress and apoptosis of placental trophoblasts. Here, we showed that palmitoleate, an omega-7 monounsaturated fatty acid, prevents ZIKV-induced ER stress and apoptosis in placental trophoblasts. Human trophoblast cell lines (JEG-3 and JAR) and normal immortalized trophoblasts (HTR-8) were used. We observed that ZIKV infection of the trophoblasts resulted in apoptosis and treatment of palmitoleate to ZIKV-infected cells significantly prevented apoptosis. However, palmitate (saturated fatty acid) did not offer protection from ZIKV-induced ER stress and apoptosis. We also observed that the Zika viral RNA copies were decreased, and the cell viability improved in ZIKV-infected cells treated with palmitoleate as compared to the infected cells without palmitoleate treatment. Further, palmitoleate was shown to protect against ZIKV-induced upregulation of ER stress markers, C/EBP homologous protein and X-box binding protein-1 splicing in placental trophoblasts. In conclusion, our studies suggest that palmitoleate protects placental trophoblasts against ZIKV-induced ER stress and apoptosis.

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“…The risk of congenital Zika infection is highest early in pregnancy (first trimester) [ 113 ]. Infants infected with ZKV develop important damage on various tissues including the central nervous system; this results in intrauterine growth retardation with stillbirths, and increased infant mortality 2 to 3 days postpartum [ 114 ]. Zika RNA has also been found in breast milk of ZKV-infected mothers [ 115 ].…”

Section: Maternal Nutrition and Lifestyle For Healthy Pregnanciesmentioning

confidence: 99%

Impact of maternal nutrition in viral infections during pregnancy

Mate

Reyes-Goya

Santana-Garrido

et al. 2021

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Other than being a physiological process, pregnancy is a condition characterized by major adaptations of maternal endocrine and metabolic homeostasis that are necessary to accommodate the fetoplacental unit. Unfortunately, all these systemic, cellular, and molecular changes in maternal physiology also make the mother and the fetus more prone to adverse outcomes, including numerous alterations arising from viral infections. Common infections during pregnancy that have long been recognized as congenitally and perinatally transmissible to newborns include toxoplasmosis, rubella, cytomegalovirus, and herpes simplex viruses (originally coined as ToRCH infections). In addition, enterovirus, parvovirus B19, hepatitis virus, varicella-zoster virus, human immunodeficiency virus, Zika and Dengue virus, and, more recently, coronavirus infections including Middle Eastern respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) infections (especially the novel SARS-CoV-2 responsible for the ongoing COVID-19 pandemic), constitute relevant targets for current research on maternal-fetal interactions in viral infections during pregnancy. Appropriate maternal education from preconception to the early postnatal period is crucial to promote healthy pregnancies in general and to prevent and/or reduce the impact of viral infections in particular. Specifically, an adequate lifestyle based on proper nutrition plans and feeding interventions, whenever possible, might be crucial to reduce the risk of virus-related gestational diseases and accompanying complications in later life. Here we aim to provide an overview of the emerging literature addressing the impact of nutrition in the context of potentially harmful viral infections during pregnancy.

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Zika virus infection induces endoplasmic reticulum stress and apoptosis in placental trophoblasts

Cited by 29 publications

References 82 publications

The Dual Regulation of Apoptosis by Flavivirus

The Dual Regulation of Apoptosis by Flavivirus

Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis

Impact of maternal nutrition in viral infections during pregnancy

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