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Principal Investigator: YUPING WANG
Organization: LOUISIANA STATE UNIV HSC SHREVEPORT
Fiscal Year: 2023
Award: $219,000
Funding agency: National Institute of Allergy and Infectious Diseases
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as the
greatest threat to global health and significantly impact pregnant women worldwide. COVID-19 infection during
pregnancy is associated with substantial risk of increases in maternal morbidity and mortality and neonatal
complications, compared with their non-infected pregnant counterparts. However, vertical transmission of the
virus is uncommon, which suggest that innate immune system must function at the maternal-fetal interface to
shield the developing fetus from infection. Despite fast-tracked intensive research on many aspects of SARS-
CoV-2, the impact of the viral infection in the placenta and the placental defense mechanism(s) are poorly
explored. Placenta is the structural and immunological barrier of pathogen transmission. To explore the innate
antiviral defense mechanism(s), in our preliminary study we specifically determined expression of interferon
pathway-related molecules in placental tissues. Strikingly, we found distinct patterns of stimulator of interferon
genes (STING), interferon regulator factor 3 (IRF3), and Type I IFN (such as IFNb) expression at the maternal-
fetal interface of the placentas from women infected with COVID-19. STING is a sensor for viral infection.
STING-IRF3 pathway signaling regulates Type I IFN production, and Type I IFNs are potent antiviral cytokines.
We also noticed that Toll-like receptor 7 (TLR7) is upregulated in both syncytiotrophoblasts (
STs) and
extravillous trophoblasts (EVTs) in placentas from patients with COVID-19 compared to those are not. TLR7,
located on the X chromosome, is a sensor for single strand RNA (ssRNA) viruses. These findings are intriguing
and indicate that an innate antiviral immune system is activated at the maternal-fetal interface in patients with
COVID-19 during pregnancy. The objective of the study is to identify spatiotemporal transcriptomic signatures
and networks of the innate antiviral immune system at the maternal-fetal interface. We will test the hypothesis
an effective and robust innate antiviral immune system is activated at the maternal-fetal interface to prevent
viral transmission and shield the fetus from infection, which will be tested in two specific aims.
Aim 1 will
identify spatiotemporal innate immunity gene profiles and networks in villous tissue that respond to maternal
SARS-CoV-2 infection. Aim 2 will identify spatiotemporal innate immunity gene profiles and networks in fetal
membrane and decidual tissue that respond to maternal SARS-CoV-2 infection. A state-of-the-art novel
technique of 10x Genomics Visium Gene Expression assay in placental formalin-fixed paraffin embedded
(FFPE) tissues combined with RNA-seq will be employed
. Placentas from women with active COVID infection,
recovered from COVID infection, and received COVID vaccination, etc. will be studied. This novel ideal
approach will allow us to map the whole transcriptome with morphological context in placental FFPE tissue and
discover the cellular and molecular profiles and networks in different cell types and gene activity at the
maternal-fetal interface without disruption of the tissue integrity. Results of the study will provide novel insights
into how
SARS-CoV-2 infection
impacts the innate immune system at the mater-fetal interface, and how the
innate immune system at the maternal-fetal interface responds to COVID vaccination during pregnancy, which
may help to identify new strategies to prevent COVID-19 infection and reduce maternal and fetal complications
in women with COVID-19 infection in the future.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><Autoregulation><Body Tissues><Brain><Brain Nervous System><COVID><COVID infected patient><COVID patient><COVID positive patient><COVID-19><COVID-19 S protein><COVID-19 infected patient><COVID-19 infection><COVID-19 patient><COVID-19 positive patient><COVID-19 prevention><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 vaccination><COVID-19 virus><COVID-19 virus infection><COVID19><COVID19 S protein><COVID19 infection><COVID19 patient><COVID19 positive patient><COVID19 prevention><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 vaccination><COVID19 virus><CV-19><CV19><Cell Body><Cells><Cells Placenta-Tissue><Cerebrum><Clinical Management><CoV disease><CoV-2><CoV2><Decidual Cell><Defense Mechanisms><Developing fetus><EPH Gestosis><Embryo><Embryonic><Encephalon><Endogenous Interferon Beta><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology Research><Epithelial Cells><Female Groups><Fetal Development><Fetal Membranes><Fetus><Fibroblast Interferon><Formalin><Future><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profiling><Genes><Genomics><Gestation><Gestational Diabetes><Gestational Diabetes Mellitus><Homeostasis><IFN><IFN-Beta><IFN-β><IFNb><Immune><Immune system><Immunes><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Infection><Innate Immune System><Innate Immunity><Interferon-beta><Interferon-β><Interferons><International><Low Birth Weight Infant><Maps><Maternal Mortality><Maternal-Fetal Exchange><Mesenchymal><Molecular><Molecular Fingerprinting><Molecular Profiling><Morphology><Native Immunity><Natural Immunity><Natural Interferon Beta><Natural human interferon beta><Neonatal><Non-Specific Immunity><Nonspecific Immunity><Normal Placentoma><Nucleic Acids><Nucleocapsid Proteins><Organ><Organoids><Outcome><Paraffin Embedding><Pathway interactions><Pattern><Physiological Homeostasis><Placenta><Placenta Embryonic Tissue><Placentome><Pre-Eclampsia><Preeclampsia><Pregnancy><Pregnancy Toxemias><Pregnancy-Induced Diabetes><Pregnant Women><Premature Birth><Prematurely delivering><Preterm Birth><Prevent viral transmission><Production><Proteins><Proteinuria-Edema-Hypertension Gestosis><RNA Seq><RNA Viruses><RNA sequencing><RNAseq><Research><Risk><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 vaccination><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 infection><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome related corona virus 2><Signal Pathway><Signal Transduction Pathway><Stimulator of Interferon Genes><Stromal Cells><Symptoms><Syncytiotrophoblast><System><TLR7><TLR7 gene><Techniques><Testing><Tissue Embedding><Tissues><Toll-Like Receptor 7><Transcript Expression Analyses><Transcript Expression Analysis><Transmission><Transplacental Exposure><Vaccination><Vertical Transmission><Villous><Viral><Viral Diseases><Virus Diseases><Woman><Women's Group><Wuhan coronavirus><X Chromosome><adverse pregnancy outcome><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after infection by SARS-CoV-2><after severe acute respiratory distress syndrome CoV-2 infection><analyze gene expression><cGAMP STING><cGAMP-STING><cGAMP/STING><cGAS/STING><cell type><cerebral><corona virus disease><corona virus disease 2019><coronavirus disease><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 prevention><coronavirus disease 2019 spike 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delivery><prevent COVID-19><prevent COVID19><prevent coronavirus disease 2019><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><psychological defense mechanism><response><sensor><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><spatiotemporal><stillbirth><stillborn><transcriptional profiling><transcriptome><transcriptome sequencing><transcriptomic sequencing><transcriptomics><transmission process><trophoblast><vaccinate against COVID-19><vaccinate against COVID19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome 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