The placenta provides a significant physical and physiological barrier to prevent fetal infection during pregnancy. Nevertheless, it is at times breached by pathogens and leads to vertical transmission of infection from mother to fetus. This review will focus specifically on the Zika flavivirus, the HIV retrovirus and the emerging SARS-CoV2 coronavirus, which have affected pregnant women and their offspring in recent epidemics. In particular, we will address how viral infections affect the immune response at the maternal-fetal interface and how the placental barrier is physically breached and discuss the consequences of infection on various aspects of placental function to support fetal growth and development. Improved understanding of how the placenta responds to viral infections will lay the foundation for developing therapeutics to these and emergent viruses, to minimise the harms of infection to the offspring.
- Klíčová slova
- Barrier function, Human immunodeficiency virus, Immune cells, Placenta, Pregnancy, Severe acute respiratory syndrome coronavirus 2, Syncytiotrophoblast, Viral infections, Zika virus,
- MeSH
- COVID-19 metabolismus MeSH
- HIV infekce metabolismus MeSH
- HIV-1 patogenita MeSH
- infekce virem zika metabolismus MeSH
- infekční komplikace v těhotenství epidemiologie virologie MeSH
- lidé MeSH
- placenta metabolismus virologie MeSH
- plod virologie MeSH
- SARS-CoV-2 patogenita MeSH
- těhotenství MeSH
- vertikální přenos infekce statistika a číselné údaje MeSH
- virové nemoci patofyziologie MeSH
- virus zika patogenita MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
An estimated 1.3 million pregnant women were living with HIV in 2018. HIV infection is associated with adverse pregnancy outcomes and all HIV-positive pregnant women, regardless of their clinical stage, should receive a combination of antiretroviral drugs to suppress maternal viral load and prevent vertical fetal infection. Although antiretroviral treatment in pregnant women has undoubtedly minimized mother-to-child transmission of HIV, several uncertainties remain. For example, while pregnancy is accompanied by changes in pharmacokinetic parameters, relevant data from clinical studies are lacking. Similarly, long-term adverse effects of exposure to antiretrovirals on fetuses have not been studied in detail. Here, we review current knowledge on HIV effects on the placenta and developing fetus, recommended antiretroviral regimens, and pharmacokinetic considerations with particular focus on placental transport. We also discuss recent advances in antiretroviral research and potential effects of antiretroviral treatment on placental/fetal development and programming.
- Klíčová slova
- Antiretroviral therapy, Fetal programming, HIV, Mother-to-child transmission, Placental membrane transporters, Placental/fetal development,
- MeSH
- antiretrovirové látky farmakologie MeSH
- HIV infekce farmakoterapie přenos MeSH
- infekční komplikace v těhotenství farmakoterapie virologie MeSH
- lidé MeSH
- placenta virologie MeSH
- těhotenství MeSH
- vertikální přenos infekce prevence a kontrola MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antiretrovirové látky MeSH
AIMS: Coronavirus disease 2019 is responsible for a worldwide increase in morbidity and mortality. The relationship of this infection to mother-to-child vertical transmission has not been elucidated yet. However, recent reports indicate a foetal death rate of up to 3%. METHODS: We report a case of sudden pre-term foetal demise in a woman positive for SARS-CoV-2 but asymptomatic, with physiological course of pregnancy. RESULTS: One of the possible explanations of sudden foetal death may be acute placental insufficiency caused by a SARS-CoV-2 placental infection or the development of foetal inflammatory response syndrome (FIRS). CONCLUSION: Considering the potential risk of foetal demise, questions remain regarding foetal monitoring and the timing of labour and delivery in the second and third trimesters, particularly in asymptomatic or mild maternal SARS-CoV-2 infection. A relevant multidisciplinary team must also be aware of these risks associated with possibly fatal consequences.
- Klíčová slova
- COVID-19, SARS-CoV-2, foetal demise, placenta,
- MeSH
- COVID-19 virologie MeSH
- dospělí MeSH
- infekční komplikace v těhotenství virologie MeSH
- lidé MeSH
- odumření plodu * MeSH
- placenta virologie MeSH
- SARS-CoV-2 izolace a purifikace MeSH
- těhotenství MeSH
- vertikální přenos infekce MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
BACKGROUND: Human Syncytin-1 is a placentally-expressed cell surface glycoprotein of retroviral origin. After interaction with ASCT2, its cellular receptor, Syncytin-1 triggers cell-cell fusion and formation of a multinuclear syncytiotrophoblast layer of the placenta. The ASCT2 receptor is a multi-spanning membrane protein containing a protruding extracellular part called region C, which has been suggested to be a retrovirus docking site. Precise identification of the interaction site between ASCT2 and Syncytin-1 is challenging due to the complex structure of ASCT2 protein and the background of endogenous ASCT2 gene in the mammalian genome. Chicken cells lack the endogenous background and, therefore, can be used to set up a system with surrogate expression of the ASCT2 receptor. RESULTS: We have established a retroviral heterologous chicken system for rapid and reliable assessment of ectopic human ASCT2 protein expression. Our dual-fluorescence system proved successful for large-scale screening of mutant ASCT2 proteins. Using this system, we demonstrated that progressive deletion of region C substantially decreased the amount of ASCT2 protein. In addition, we implemented quantitative assays to determine the interaction of ASCT2 with Syncytin-1 at multiple levels, which included binding of the soluble form of Syncytin-1 to ASCT2 on the cell surface and a luciferase-based assay to evaluate cell-cell fusions that were triggered by Syncytin-1. Finally, we restored the envelope function of Syncytin-1 in a replication-competent retrovirus and assessed the infection of chicken cells expressing human ASCT2 by chimeric Syncytin-1-enveloped virus. The results of the quantitative assays showed that deletion of the protruding region C did not abolish the interaction of ASCT2 with Syncytin-1. CONCLUSIONS: We present here a heterologous chicken system for effective assessment of the expression of transmembrane ASCT2 protein and its interaction with Syncytin-1. The system profits from the absence of endogenous ASCT2 background and implements the quantitative assays to determine the ASCT2-Syncytin-1 interaction at several levels. Using this system, we demonstrated that the protruding region C was essential for ASCT2 protein expression, but surprisingly, not for the interaction with Syncytin-1 glycoprotein.
- Klíčová slova
- ASCT2 (SLC1A5), Cell–cell fusion, Envelope glycoprotein, Envelope-receptor interaction, NanoLuc luciferase, Retroviral receptor, Syncytin-1,
- MeSH
- buněčné linie MeSH
- fibroblasty virologie MeSH
- fluorescence MeSH
- genové produkty env genetika metabolismus MeSH
- konfokální mikroskopie MeSH
- kur domácí MeSH
- lidé MeSH
- placenta virologie MeSH
- těhotenské proteiny genetika metabolismus MeSH
- těhotenství MeSH
- transportní systém ASC pro aminokyseliny genetika metabolismus MeSH
- vedlejší histokompatibilní antigeny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- genové produkty env MeSH
- SLC1A5 protein, human MeSH Prohlížeč
- syncytin MeSH Prohlížeč
- těhotenské proteiny MeSH
- transportní systém ASC pro aminokyseliny MeSH
- vedlejší histokompatibilní antigeny MeSH
