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Carolyn Coyne

George Barth Geller Distinguished Professor of Immunology
Integrative Immunobiology
3130 MSRB III, Box 3054, Durham, NC 27710
3130 MSRB III BX 3054, 3 Genome Court, Durham, NC 27710

Selected Publications


The trophoblast surface becomes refractory to adhesion by congenitally transmitted Toxoplasma gondii and Listeria monocytogenes during cytotrophoblast to syncytiotrophoblast development.

Journal Article mSphere · May 21, 2024 The placenta is a critical barrier against viral, bacterial, and eukaryotic pathogens. For most teratogenic pathogens, the precise molecular mechanisms of placental resistance are still being unraveled. Given the importance of understanding these mechanism ... Full text Link to item Cite

Trophoblast organoids with physiological polarity model placental structure and function.

Journal Article J Cell Sci · March 1, 2024 Human trophoblast organoids (TOs) are a three-dimensional ex vivo culture model that can be used to study various aspects of placental development, physiology and pathology. However, standard culturing of TOs does not recapitulate the cellular orientation ... Full text Link to item Cite

Human trophoblast stem cells can be used to model placental susceptibility to Toxoplasma gondii and highlight the critical importance of the trophoblast cell surface in pathogen resistance.

Journal Article bioRxiv · November 11, 2023 The placenta is a critical barrier against viral, bacterial, and eukaryotic pathogens. For most teratogenic pathogens, the precise molecular mechanisms of placental resistance are still being unraveled. Given the importance to understand these mechanisms a ... Full text Link to item Cite

Contemporary enterovirus-D68 isolates infect human spinal cord organoids.

Journal Article mBio · August 31, 2023 Enterovirus D68 (EV-D68) is a nonpolio enterovirus associated with severe respiratory illness and acute flaccid myelitis (AFM), a polio-like illness causing paralysis in children. AFM outbreaks have been associated with increased circulation and genetic di ... Full text Link to item Cite

Pregnancy-associated morbidity and mortality during pandemics: Looking to the past in order to prepare for the future.

Journal Article Cell Host Microbe · June 14, 2023 Pregnant women are at high risk of adverse outcomes in the setting of viral-associated outbreaks and pandemics. In this forum, we discuss the impact of past and current pandemics on pregnant women and make recommendations to protect this vulnerable populat ... Full text Link to item Cite

Cellular glycan modification by B3GAT1 broadly restricts influenza virus infection.

Journal Article Nat Commun · October 29, 2022 Communicable respiratory viral infections pose both epidemic and pandemic threats and broad-spectrum antiviral strategies could improve preparedness for these events. To discover host antiviral restriction factors that may act as suitable targets for the d ... Full text Link to item Cite

Evolution and antiviral activity of a human protein of retroviral origin.

Journal Article Science · October 28, 2022 Endogenous retroviruses are abundant components of mammalian genomes descended from ancient germline infections. In several mammals, the envelope proteins encoded by these elements protect against exogenous viruses, but this activity has not been documente ... Full text Link to item Cite

Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface.

Journal Article Elife · August 17, 2022 Infections at the maternal-fetal interface can directly harm the fetus and induce complications that adversely impact pregnancy outcomes. Innate immune signaling by both fetal-derived placental trophoblasts and the maternal decidua must provide antimicrobi ... Full text Link to item Cite

An In Vivo Model of Echovirus-Induced Meningitis Defines the Differential Roles of Type I and Type III Interferon Signaling in Central Nervous System Infection.

Journal Article J Virol · July 13, 2022 Echoviruses are among the most common worldwide causes of aseptic meningitis, which can cause long-term sequelae and death, particularly in neonates. However, the mechanisms by which these viruses induce meningeal inflammation are poorly understood, owing ... Full text Link to item Cite

Functional coupling between TRPV4 channel and TMEM16F modulates human trophoblast fusion.

Journal Article Elife · June 7, 2022 TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), is critical for placental trophoblast syncytialization, HIV infection, and SARS-CoV2-mediated syncytialization, however, how TMEM16F is activated during cell fusion is unclear. Here, using troph ... Full text Open Access Link to item Cite

Enterovirus Replication and Dissemination Are Differentially Controlled by Type I and III Interferons in the Gastrointestinal Tract.

Journal Article mBio · June 2022 Enteroviruses are among the most common viral infectious agents of humans and cause a broad spectrum of mild-to-severe illness. Enteroviruses are transmitted primarily by the fecal-oral route, but the events associated with their intestinal replication ... Full text Cite

Infections at the maternal-fetal interface: an overview of pathogenesis and defence.

Journal Article Nat Rev Microbiol · February 2022 Infections are a major threat to human reproductive health, and infections in pregnancy can cause prematurity or stillbirth, or can be vertically transmitted to the fetus leading to congenital infection and severe disease. The acronym 'TORCH' (Toxoplasma g ... Full text Link to item Cite

Innate immune defenses at the maternal-fetal interface.

Journal Article Curr Opin Immunol · February 2022 The human maternal-fetal interface is an immunologically complex environment that must balance the divergent demands of tolerance towards the developing fetus with anti-pathogen defense. The innate immune responses at the maternal-fetal interface that func ... Full text Link to item Cite

Enteroviruses: The role of receptors in viral pathogenesis.

Journal Article Adv Virus Res · 2022 Enteroviruses are among the most common viral infectious agents of humans and cause a broad spectrum of illness, which can range from mild and self-limiting to severe. Severe outcomes of enteroviral infections can include aseptic meningitis, bronchitis, ac ... Full text Link to item Cite

Toxoplasma gondii GRA28 Is Required for Placenta-Specific Induction of the Regulatory Chemokine CCL22 in Human and Mouse.

Journal Article mBio · December 21, 2021 Toxoplasma gondii is an intracellular protozoan pathogen of humans that can cross the placenta and result in adverse pregnancy outcomes and long-term birth defects. The mechanisms used by T. gondii to cross the placenta are unknown, but complex interaction ... Full text Link to item Cite

A standardized definition of placental infection by SARS-CoV-2, a consensus statement from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development SARS-CoV-2 Placental Infection Workshop.

Journal Article Am J Obstet Gynecol · December 2021 Pregnant individuals infected with SARS-CoV-2 have higher rates of intensive care unit admission, oxygen requirement, need for mechanical ventilation, and death than nonpregnant individuals. Increased COVID-19 disease severity may be associated with an inc ... Full text Link to item Cite

Pregnancy influences immune responses to SARS-CoV-2.

Journal Article Sci Transl Med · October 27, 2021 Pregnancy and fetal sex influence the quality of antibody responses to SARS-CoV-2 infection and immunization (Atyeo et al., Bordt et al.). ... Full text Link to item Cite

The trophoblast surface becomes refractory to adhesion by congenitally transmitted Toxoplasma gondii and Listeria monocytogenes during cytotrophoblast to syncytiotrophoblast development.

Journal Article mSphere · May 21, 2024 The placenta is a critical barrier against viral, bacterial, and eukaryotic pathogens. For most teratogenic pathogens, the precise molecular mechanisms of placental resistance are still being unraveled. Given the importance of understanding these mechanism ... Full text Link to item Cite

Trophoblast organoids with physiological polarity model placental structure and function.

Journal Article J Cell Sci · March 1, 2024 Human trophoblast organoids (TOs) are a three-dimensional ex vivo culture model that can be used to study various aspects of placental development, physiology and pathology. However, standard culturing of TOs does not recapitulate the cellular orientation ... Full text Link to item Cite

Human trophoblast stem cells can be used to model placental susceptibility to Toxoplasma gondii and highlight the critical importance of the trophoblast cell surface in pathogen resistance.

Journal Article bioRxiv · November 11, 2023 The placenta is a critical barrier against viral, bacterial, and eukaryotic pathogens. For most teratogenic pathogens, the precise molecular mechanisms of placental resistance are still being unraveled. Given the importance to understand these mechanisms a ... Full text Link to item Cite

Contemporary enterovirus-D68 isolates infect human spinal cord organoids.

Journal Article mBio · August 31, 2023 Enterovirus D68 (EV-D68) is a nonpolio enterovirus associated with severe respiratory illness and acute flaccid myelitis (AFM), a polio-like illness causing paralysis in children. AFM outbreaks have been associated with increased circulation and genetic di ... Full text Link to item Cite

Pregnancy-associated morbidity and mortality during pandemics: Looking to the past in order to prepare for the future.

Journal Article Cell Host Microbe · June 14, 2023 Pregnant women are at high risk of adverse outcomes in the setting of viral-associated outbreaks and pandemics. In this forum, we discuss the impact of past and current pandemics on pregnant women and make recommendations to protect this vulnerable populat ... Full text Link to item Cite

Cellular glycan modification by B3GAT1 broadly restricts influenza virus infection.

Journal Article Nat Commun · October 29, 2022 Communicable respiratory viral infections pose both epidemic and pandemic threats and broad-spectrum antiviral strategies could improve preparedness for these events. To discover host antiviral restriction factors that may act as suitable targets for the d ... Full text Link to item Cite

Evolution and antiviral activity of a human protein of retroviral origin.

Journal Article Science · October 28, 2022 Endogenous retroviruses are abundant components of mammalian genomes descended from ancient germline infections. In several mammals, the envelope proteins encoded by these elements protect against exogenous viruses, but this activity has not been documente ... Full text Link to item Cite

Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface.

Journal Article Elife · August 17, 2022 Infections at the maternal-fetal interface can directly harm the fetus and induce complications that adversely impact pregnancy outcomes. Innate immune signaling by both fetal-derived placental trophoblasts and the maternal decidua must provide antimicrobi ... Full text Link to item Cite

An In Vivo Model of Echovirus-Induced Meningitis Defines the Differential Roles of Type I and Type III Interferon Signaling in Central Nervous System Infection.

Journal Article J Virol · July 13, 2022 Echoviruses are among the most common worldwide causes of aseptic meningitis, which can cause long-term sequelae and death, particularly in neonates. However, the mechanisms by which these viruses induce meningeal inflammation are poorly understood, owing ... Full text Link to item Cite

Functional coupling between TRPV4 channel and TMEM16F modulates human trophoblast fusion.

Journal Article Elife · June 7, 2022 TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), is critical for placental trophoblast syncytialization, HIV infection, and SARS-CoV2-mediated syncytialization, however, how TMEM16F is activated during cell fusion is unclear. Here, using troph ... Full text Open Access Link to item Cite

Enterovirus Replication and Dissemination Are Differentially Controlled by Type I and III Interferons in the Gastrointestinal Tract.

Journal Article mBio · June 2022 Enteroviruses are among the most common viral infectious agents of humans and cause a broad spectrum of mild-to-severe illness. Enteroviruses are transmitted primarily by the fecal-oral route, but the events associated with their intestinal replication ... Full text Cite

Infections at the maternal-fetal interface: an overview of pathogenesis and defence.

Journal Article Nat Rev Microbiol · February 2022 Infections are a major threat to human reproductive health, and infections in pregnancy can cause prematurity or stillbirth, or can be vertically transmitted to the fetus leading to congenital infection and severe disease. The acronym 'TORCH' (Toxoplasma g ... Full text Link to item Cite

Innate immune defenses at the maternal-fetal interface.

Journal Article Curr Opin Immunol · February 2022 The human maternal-fetal interface is an immunologically complex environment that must balance the divergent demands of tolerance towards the developing fetus with anti-pathogen defense. The innate immune responses at the maternal-fetal interface that func ... Full text Link to item Cite

Enteroviruses: The role of receptors in viral pathogenesis.

Journal Article Adv Virus Res · 2022 Enteroviruses are among the most common viral infectious agents of humans and cause a broad spectrum of illness, which can range from mild and self-limiting to severe. Severe outcomes of enteroviral infections can include aseptic meningitis, bronchitis, ac ... Full text Link to item Cite

Toxoplasma gondii GRA28 Is Required for Placenta-Specific Induction of the Regulatory Chemokine CCL22 in Human and Mouse.

Journal Article mBio · December 21, 2021 Toxoplasma gondii is an intracellular protozoan pathogen of humans that can cross the placenta and result in adverse pregnancy outcomes and long-term birth defects. The mechanisms used by T. gondii to cross the placenta are unknown, but complex interaction ... Full text Link to item Cite

A standardized definition of placental infection by SARS-CoV-2, a consensus statement from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development SARS-CoV-2 Placental Infection Workshop.

Journal Article Am J Obstet Gynecol · December 2021 Pregnant individuals infected with SARS-CoV-2 have higher rates of intensive care unit admission, oxygen requirement, need for mechanical ventilation, and death than nonpregnant individuals. Increased COVID-19 disease severity may be associated with an inc ... Full text Link to item Cite

Pregnancy influences immune responses to SARS-CoV-2.

Journal Article Sci Transl Med · October 27, 2021 Pregnancy and fetal sex influence the quality of antibody responses to SARS-CoV-2 infection and immunization (Atyeo et al., Bordt et al.). ... Full text Link to item Cite

Respiratory and intestinal epithelial cells exhibit differential susceptibility and innate immune responses to contemporary EV-D68 isolates.

Journal Article Elife · July 1, 2021 Enterovirus D68 (EV-D68) has been implicated in outbreaks of severe respiratory illness and is associated with acute flaccid myelitis (AFM). EV-D68 is often detected in patient respiratory samples but has also been detected in stool and wastewater, suggest ... Full text Link to item Cite

Uterine NK cell education: Learning the ropes in pregnancy.

Journal Article Immunity · June 8, 2021 The impact of inhibitory receptor NKG2A-mediated education on uterine NK (uNK) cell responsiveness to vascular remodeling on pregnancy outcomes has remained unclear. In this issue of Immunity, Shreeve et al. show that loss of NKG2A+ uNK cells results in de ... Full text Link to item Cite

BPIFB3 interacts with ARFGAP1 and TMED9 to regulate non-canonical autophagy and RNA virus infection.

Journal Article J Cell Sci · February 25, 2021 Autophagy is a degradative cellular pathway that targets cytoplasmic contents and organelles for turnover by the lysosome. Various autophagy pathways play key roles in the clearance of viral infections, and many families of viruses have developed unique me ... Full text Link to item Cite

Gatekeepers of the fetus: Characterization of placental macrophages.

Journal Article J Exp Med · January 4, 2021 In this issue of JEM, Thomas et al. (https://doi.org/10.1084/jem.20200891) provide elegant technological and conceptual advances that further our understanding of the immune cells enriched at the maternal-fetal interface. Using new isolation strategies to ... Full text Open Access Link to item Cite

Inflammasome signaling in human placental trophoblasts regulates immune defense against Listeria monocytogenes infection.

Journal Article J Exp Med · January 4, 2021 The human placenta is a dynamic organ that modulates physiological adaptations to pregnancy. To define the immunological signature of the human placenta, we performed unbiased profiling of secreted immune factors from human chorionic villi isolated from pl ... Full text Open Access Link to item Cite

Human FcRn expression and Type I Interferon signaling control Echovirus 11 pathogenesis in mice.

Journal Article PLoS Pathog · January 2021 Neonatal echovirus infections are characterized by severe hepatitis and neurological complications that can be fatal. Here, we show that expression of the human homologue of the neonatal Fc receptor (hFcRn), the primary receptor for echoviruses, and ablati ... Full text Link to item Cite

The Role of Congenital Cytomegalovirus Infection in Adverse Birth Outcomes: A Review of the Potential Mechanisms.

Journal Article Viruses · December 24, 2020 Human cytomegalovirus (CMV) is a major cause of nonhereditary adverse birth outcomes, including hearing and visual loss, neurologic deficits, and intrauterine growth retardation (IUGR), and may contribute to outcomes such as stillbirth and preterm delivery ... Full text Open Access Link to item Cite

Dengue Virus Targets Nrf2 for NS2B3-Mediated Degradation Leading to Enhanced Oxidative Stress and Viral Replication.

Journal Article J Virol · November 23, 2020 Dengue virus (DENV) is a mosquito-borne virus that infects upward of 300 million people annually and has the potential to cause fatal hemorrhagic fever and shock. While the parameters contributing to dengue immunopathogenesis remain unclear, the collapse o ... Full text Link to item Cite

Unc-13 homolog D mediates an antiviral effect of the chromosome 19 microRNA cluster miR-517a.

Journal Article J Cell Sci · November 19, 2020 The function of microRNAs (miRNAs) can be cell autonomous or communicated to other cell types and has been implicated in diverse biological processes. We previously demonstrated that miR-517a-3p (miR-517a), a highly expressed member of the chromosome 19 mi ... Full text Link to item Cite

Imaging-Based Reporter Systems to Define CVB-Induced Membrane Remodeling in Living Cells.

Journal Article Viruses · September 25, 2020 Enteroviruses manipulate host membranes to form replication organelles, which concentrate viral and host factors to allow for efficient replication. However, this process has not been well-studied in living cells throughout the course of infection. To defi ... Full text Open Access Link to item Cite

Recommendations for future university pandemic responses: What the first COVID-19 shutdown taught us.

Journal Article PLoS Biol · August 2020 The SARS-CoV-2 epidemic challenged universities and other academic institutions to rapidly adapt to urgent and life-threatening situations. It forced most institutions to shut down nearly every aspect of their research and educational enterprises. In doing ... Full text Open Access Link to item Cite

Cell type- and species-specific host responses to Toxoplasma gondii and its near relatives.

Journal Article Int J Parasitol · May 2020 Toxoplasma gondii is remarkably unique in its ability to successfully infect vertebrate hosts from multiple phyla and can successfully infect most cells within these organisms. The infection outcome in each of these species is determined by the complex int ... Full text Open Access Link to item Cite

BPIFB3 Regulates Endoplasmic Reticulum Morphology To Facilitate Flavivirus Replication.

Journal Article J Virol · April 16, 2020 Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), rely heavily on the availability of endoplasmic reticulum (ER) membranes throughout their life cycle, and degradation of ER membranes restricts flavivirus replication. Accordingly, DENV and ... Full text Link to item Cite

An Evolutionary Insertion in the Mxra8 Receptor-Binding Site Confers Resistance to Alphavirus Infection and Pathogenesis.

Journal Article Cell Host Microbe · March 11, 2020 Alphaviruses are emerging, mosquito-transmitted RNA viruses with poorly understood cellular tropism and species selectivity. Mxra8 is a receptor for multiple alphaviruses including chikungunya virus (CHIKV). We discovered that while expression of mouse, ra ... Full text Open Access Link to item Cite

Enteroviruses: A Gut-Wrenching Game of Entry, Detection, and Evasion.

Journal Article Viruses · May 21, 2019 Enteroviruses are a major source of human disease, particularly in neonates and young children where infections can range from acute, self-limited febrile illness to meningitis, endocarditis, hepatitis, and acute flaccid myelitis. The enterovirus genus inc ... Full text Open Access Link to item Cite

B-101 Placental exosomes in maternal-placental-fetal communication and viral resistance

Conference JAIDS Journal of Acquired Immune Deficiency Syndromes · April 2019 The placenta plays a critical role in regulating maternal-fetal gas exchange, supply of nutrients to the fetus and removal of waste, production of hormones, and immunological defense, including resistance to diverse pathogens. While many of these f ... Full text Cite

Type III interferon signaling restricts enterovirus 71 infection of goblet cells.

Journal Article Sci Adv · March 2019 Recent worldwide outbreaks of enterovirus 71 (EV71) have caused major epidemics of hand, foot, and mouth disease with severe neurological complications, including acute flaccid paralysis. EV71 is transmitted by the enteral route, but little is known about ... Full text Link to item Cite

The neonatal Fc receptor is a pan-echovirus receptor.

Journal Article Proc Natl Acad Sci U S A · February 26, 2019 Echoviruses are amongst the most common causative agents of aseptic meningitis worldwide and are particularly devastating in the neonatal population, where they are associated with severe hepatitis, neurological disease, including meningitis and encephalit ... Full text Link to item Cite

Emerging arboviruses and implications for pediatric transplantation: A review.

Journal Article Pediatr Transplant · February 2019 Recent years have brought a rise in newly emergent viral infections, primarily in the form of previously known arthropod-transmitted viruses that have increased significantly in both incidence and geographical range. Of particular note are DENV, CHIKV, and ... Full text Open Access Link to item Cite

Interferon lambda protects the female reproductive tract against Zika virus infection.

Journal Article Nat Commun · January 17, 2019 Although Zika virus (ZIKV) can be transmitted sexually and cause congenital birth defects, immune control mechanisms in the female reproductive tract (FRT) are not well characterized. Here we show that treatment of primary human vaginal and cervical epithe ... Full text Link to item Cite

RIPK3: Beyond Necroptosis.

Journal Article Immunity · January 15, 2019 In this issue of Immunity, Daniels et al. (2019) demonstrate that RIPK3 signaling limits Zika virus (ZIKV) infection in the central nervous system independently of its function in necroptosis by promoting itaconate production in infected neurons, thereby r ... Full text Open Access Link to item Cite

Immune responses at the maternal-fetal interface.

Journal Article Sci Immunol · January 11, 2019 Pregnancy poses an immunological challenge because a genetically distinct (nonself) fetus must be supported within the pregnant female for the required gestational period. Placentation, or the establishment of the fetally derived placenta, is a common stra ... Full text Link to item Cite

Rift Valley fever virus induces fetal demise in Sprague-Dawley rats through direct placental infection.

Journal Article Sci Adv · December 2018 Rift Valley fever virus (RVFV) infections in pregnant livestock cause high rates of fetal demise; miscarriage in pregnant women has also been associated with RVFV infection. To address how RVFV infection during pregnancy causes detrimental effects on the f ... Full text Link to item Cite

Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages.

Journal Article Cell Host Microbe · November 14, 2018 Zika virus (ZIKV), which emerged in regions endemic to dengue virus (DENV), is vertically transmitted and results in adverse pregnancy outcomes. Antibodies to DENV can cross-react with ZIKV, but whether these antibodies influence ZIKV vertical transmission ... Full text Open Access Link to item Cite

Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age.

Journal Article Infect Immun · November 2018 Tissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important i ... Full text Link to item Cite

Type III Interferons in Antiviral Defenses at Barrier Surfaces.

Journal Article Trends Immunol · October 2018 Barrier surfaces such as the epithelium lining the respiratory and gastrointestinal (GI) tracts, the endothelium comprising the blood-brain barrier (BBB), and placental trophoblasts provide key physical and immunological protection against viruses. These b ... Full text Open Access Link to item Cite

STING'ing Zika virus in neurons.

Journal Article Nat Microbiol · September 2018 Full text Open Access Link to item Cite

Stem Cell-Derived Models of Viral Infections in the Gastrointestinal Tract.

Journal Article Viruses · March 10, 2018 Studies on the intestinal epithelial response to viral infection have previously been limited by the absence of in vitro human intestinal models that recapitulate the multicellular complexity of the gastrointestinal tract. Recent technological advances hav ... Full text Open Access Link to item Cite

Zika virus-related neurotropic flaviviruses infect human placental explants and cause fetal demise in mice.

Journal Article Sci Transl Med · January 31, 2018 Although Zika virus (ZIKV) infection in pregnant women can cause placental damage, intrauterine growth restriction, microcephaly, and fetal demise, these disease manifestations only became apparent in the context of a large epidemic in the Americas. We hyp ... Full text Link to item Cite

Human Placental Syncytiotrophoblasts Restrict Toxoplasma gondii Attachment and Replication and Respond to Infection by Producing Immunomodulatory Chemokines.

Journal Article mBio · January 9, 2018 Toxoplasma gondii is a major source of congenital disease worldwide, but the cellular and molecular factors associated with its vertical transmission are largely unknown. In humans, the placenta forms the key interface between the maternal and fetal compar ... Full text Link to item Cite

Type I interferons instigate fetal demise after Zika virus infection.

Journal Article Sci Immunol · January 5, 2018 Zika virus (ZIKV) infection during pregnancy is associated with adverse fetal outcomes, including microcephaly, growth restriction, and fetal demise. Type I interferons (IFNs) are essential for host resistance against ZIKV, and IFN-α/β receptor (IFNAR)-def ... Full text Link to item Cite

The exoribonuclease Xrn1 is a post-transcriptional negative regulator of autophagy.

Journal Article Autophagy · 2018 Macroautophagy/autophagy is a conserved catabolic process that promotes survival during stress. Autophagic dysfunction is associated with pathologies such as cancer and neurodegenerative diseases. Thus, autophagy must be strictly modulated at multiple leve ... Full text Link to item Cite

Chromosome 19 microRNAs exert antiviral activity independent from type III interferon signaling.

Journal Article Placenta · January 2018 INTRODUCTION: Cultured primary human trophoblasts (PHT), derived from term placentas, are relatively resistant to infection by diverse viruses. The resistance can be conferred to non-trophoblastic cells by pre-exposing them to medium that was conditioned b ... Full text Open Access Link to item Cite

Gestational Stage and IFN-λ Signaling Regulate ZIKV Infection In Utero.

Journal Article Cell Host Microbe · September 13, 2017 Although Zika virus (ZIKV)-induced congenital disease occurs more frequently during early stages of pregnancy, its basis remains undefined. Using established type I interferon (IFN)-deficient mouse models of ZIKV transmission in utero, we found that the pl ... Full text Open Access Link to item Cite

Organotypic models of type III interferon-mediated protection from Zika virus infections at the maternal-fetal interface.

Journal Article Proc Natl Acad Sci U S A · August 29, 2017 Protecting the fetus from the hematogenous spread of viruses requires multifaceted layers of protection and relies heavily on trophoblasts, the fetal-derived cells that comprise the placental barrier. We showed previously that trophoblasts isolated from fu ... Full text Link to item Cite

Expression and trafficking of placental microRNAs at the feto-maternal interface.

Journal Article FASEB J · July 2017 During pregnancy, placental trophoblasts at the feto-maternal interface produce a broad repertoire of microRNA (miRNA) species. These species include miRNA from the primate-specific chromosome 19 miRNA cluster (C19MC), which is expressed nearly exclusively ... Full text Link to item Cite

Microbial Vertical Transmission during Human Pregnancy.

Journal Article Cell Host Microbe · May 10, 2017 Congenital infections with pathogens such as Zika virus, Toxoplasma gondii, Listeria monocytogenes, Treponema pallidium, parvovirus, HIV, varicella zoster virus, Rubella, Cytomegalovirus, and Herpesviruses are a major cause of morbidity and mortality world ... Full text Link to item Cite

The expression level of C19MC miRNAs in early pregnancy and in response to viral infection.

Journal Article Placenta · May 2017 INTRODUCTION: We have previously shown that miRNAs produced from the Chromosome 19 MiRNA Cluster (C19MC), which are expressed almost exclusively in primate trophoblasts and are released into the maternal circulation, reduce viral replication in non-placent ... Full text Link to item Cite

Enteroviruses infect human enteroids and induce antiviral signaling in a cell lineage-specific manner.

Journal Article Proc Natl Acad Sci U S A · February 14, 2017 Enteroviruses are among the most common viral infectious agents of humans and are primarily transmitted by the fecal-oral route. However, the events associated with enterovirus infections of the human gastrointestinal tract remain largely unknown. Here, we ... Full text Link to item Cite

Dengue and Zika viruses subvert reticulophagy by NS2B3-mediated cleavage of FAM134B.

Journal Article Autophagy · February 2017 The endoplasmic reticulum (ER) is exploited by several diverse viruses during their infectious life cycles. Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), utilize the ER as a source of membranes to establish their replication organelles ... Full text Link to item Cite

Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus.

Journal Article Cell Rep · January 17, 2017 Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2,000 bioactive compounds for their ability to block Zika virus infection in three distinct cell types with two differen ... Full text Link to item Cite

A Three-Dimensional Cell Culture System To Model RNA Virus Infections at the Blood-Brain Barrier.

Journal Article mSphere · 2017 The blood-brain barrier (BBB) comprises the foremost protective barrier in the brain and is composed in part of a layer of microvascular endothelial cells that line the capillaries surrounding the brain. Here, we describe a human three-dimensional (3-D) ce ... Full text Link to item Cite

Isolation of human trophoblastic extracellular vesicles and characterization of their cargo and antiviral activity.

Journal Article Placenta · November 2016 INTRODUCTION: Primary human trophoblasts release a repertoire of extracellular vesicles (EVs). Among them are nano-sized exosomes, which we found to suppress the replication of a wide range of diverse viruses. These exosomes contain trophoblastic microRNAs ... Full text Link to item Cite

Zika virus - reigniting the TORCH.

Journal Article Nat Rev Microbiol · November 2016 The recent association between Zika virus (ZIKV) infection during pregnancy and fetal microcephaly has led to a renewed interest in the mechanisms by which vertically transmitted microorganisms reach the fetus and cause congenital disease. In this Opinion ... Full text Link to item Cite

Mechanisms of Zika Virus Infection and Neuropathogenesis.

Journal Article DNA Cell Biol · August 2016 A spotlight has been focused on the mosquito-borne Zika virus (ZIKV) because of its epidemic outbreak in Brazil and Latin America, as well as the severe neurological manifestations of microcephaly and Guillain-Barré syndrome associated with infection. In t ... Full text Link to item Cite

BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication.

Journal Article J Virol · May 15, 2016 UNLABELLED: Bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) is an endoplasmic reticulum (ER)-localized host factor that negatively regulates coxsackievirus B (CVB) replication through its control of the autoph ... Full text Link to item Cite

Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection.

Journal Article Cell Host Microbe · May 11, 2016 During mammalian pregnancy, the placenta acts as a barrier between the maternal and fetal compartments. The recently observed association between Zika virus (ZIKV) infection during human pregnancy and fetal microcephaly and other anomalies suggests that ZI ... Full text Link to item Cite

MOV10 Provides Antiviral Activity against RNA Viruses by Enhancing RIG-I-MAVS-Independent IFN Induction.

Journal Article J Immunol · May 1, 2016 Moloney leukemia virus 10, homolog (MOV10) is an IFN-inducible RNA helicase, associated with small RNA-induced silencing. In this article, we report that MOV10 exhibits antiviral activity, independent of its helicase function, against a number of positive- ... Full text Link to item Cite

Innate immune signaling through differential RIPK1 expression promote tumor progression in head and neck squamous cell carcinoma.

Journal Article Carcinogenesis · May 2016 Head and neck squamous cell carcinoma (HNSCC) is a devastating disease for which new treatments, such as immunotherapy are needed. Synthetic double-stranded RNAs, which activate toll-like receptor 3 (TLR3), have been used as potent adjuvants in cancer immu ... Full text Link to item Cite

A three-dimensional culture system recapitulates placental syncytiotrophoblast development and microbial resistance.

Journal Article Sci Adv · March 2016 In eutherians, the placenta acts as a barrier and conduit at the maternal-fetal interface. Syncytiotrophoblasts, the multinucleated cells that cover the placental villous tree surfaces of the human placenta, are directly bathed in maternal blood and are fo ... Full text Open Access Link to item Cite

Respiratory syncytial virus infection enhances Pseudomonas aeruginosa biofilm growth through dysregulation of nutritional immunity.

Journal Article Proc Natl Acad Sci U S A · February 9, 2016 Clinical observations link respiratory virus infection and Pseudomonas aeruginosa colonization in chronic lung disease, including cystic fibrosis (CF) and chronic obstructive pulmonary disease. The development of P. aeruginosa into highly antibiotic-resist ... Full text Link to item Cite

A Three-Dimensional Cell Culture Model To Study Enterovirus Infection of Polarized Intestinal Epithelial Cells.

Journal Article mSphere · 2016 Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the ... Full text Open Access Link to item Cite

MicroRNAs in placental health and disease.

Journal Article Am J Obstet Gynecol · October 2015 MicroRNAs (miRNAs) constitute a large family of small noncoding RNAs that are encoded by the genomes of most organisms. They regulate gene expression through posttranscriptional mechanisms to attenuate protein output in various genetic networks. The discov ... Full text Link to item Cite

ADAP2 Is an Interferon Stimulated Gene That Restricts RNA Virus Entry.

Journal Article PLoS Pathog · September 2015 Interferon stimulated genes (ISGs) target viruses at various stages of their infectious life cycles, including at the earliest stage of viral entry. Here we identify ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2) as a gene upregulated by type ... Full text Open Access Link to item Cite

RIP3 Regulates Autophagy and Promotes Coxsackievirus B3 Infection of Intestinal Epithelial Cells.

Journal Article Cell Host Microbe · August 12, 2015 Receptor interacting protein kinase-3 (RIP3) is an essential kinase for necroptotic cell death signaling and has been implicated in antiviral cell death signaling upon DNA virus infection. Here, we performed high-throughput RNAi screening and identified RI ... Full text Link to item Cite

Autophagy modulates articular cartilage vesicle formation in primary articular chondrocytes.

Journal Article J Biol Chem · May 22, 2015 Chondrocyte-derived extracellular organelles known as articular cartilage vesicles (ACVs) participate in non-classical protein secretion, intercellular communication, and pathologic calcification. Factors affecting ACV formation and release remain poorly c ... Full text Link to item Cite

The Function of TrophomiRs and Other MicroRNAs in the Human Placenta.

Journal Article Cold Spring Harb Perspect Med · April 15, 2015 In eutherian organisms, the placenta interfaces the fetal and maternal environments. Located at the placental villous surface, in direct contact with maternal blood, is the trophoblast layer, which mediates the crucial maternal-fetal exchange of gases, nut ... Full text Link to item Cite

Unc93b Induces Apoptotic Cell Death and Is Cleaved by Host and Enteroviral Proteases.

Journal Article PLoS One · 2015 Unc93b is an endoplasmic reticulum (ER)-resident transmembrane protein that serves to bind and traffic toll-like receptors (TLRs) from the ER to their appropriate subcellular locations for ligand sensing. Because of its role in TLR trafficking, Unc93b is n ... Full text Open Access Link to item Cite

Human trophoblasts confer resistance to viruses implicated in perinatal infection.

Journal Article Am J Obstet Gynecol · January 2015 OBJECTIVE: Primary human trophoblasts were previously shown to be resistant to viral infection, and able to confer this resistance to nontrophoblast cells. Can trophoblasts protect nontrophoblastic cells from infection by viruses or other intracellular pat ... Full text Link to item Cite

BPIFB3 regulates autophagy and coxsackievirus B replication through a noncanonical pathway independent of the core initiation machinery.

Journal Article mBio · December 9, 2014 UNLABELLED: Enteroviruses require autophagy to facilitate the formation of autophagosome (AP)-like double-membrane vesicles that provide the scaffolding for RNA replication. Here, we identify bactericidal/permeability-increasing protein (BPI) fold-containi ... Full text Open Access Link to item Cite

The Placenta as a Barrier to Viral Infections.

Journal Article Annu Rev Virol · November 2014 Throughout pregnancy, the placenta acts as a physical and immunological barrier against the hematogenous transmission of viruses from mother to fetus. Despite this, very little is known regarding the specific mechanisms by which the placenta shields the de ... Full text Link to item Cite

Death waits for no man--does it wait for a virus? How enteroviruses induce and control cell death.

Journal Article Cytokine Growth Factor Rev · October 2014 Enteroviruses (EVs) are the most common human viral pathogens. They cause a variety of pathologies, including myocarditis and meningoencephalopathies, and have been linked to the onset of type I diabetes. These pathologies result from the death of cells in ... Full text Link to item Cite

Antiviral activity of human OASL protein is mediated by enhancing signaling of the RIG-I RNA sensor.

Journal Article Immunity · June 19, 2014 Virus infection is sensed in the cytoplasm by retinoic acid-inducible gene I (RIG-I, also known as DDX58), which requires RNA and polyubiquitin binding to induce type I interferon (IFN) and activate cellular innate immunity. We show that the human IFN-indu ... Full text Link to item Cite

Review: placenta-specific microRNAs in exosomes - good things come in nano-packages.

Journal Article Placenta · February 2014 MicroRNAs (miRNAs) are small noncoding RNA gene products that commonly regulate mRNA expression by repression of translation and/or transcript decay. Whereas common and unique types of miRNAs are expressed by the placenta during pregnancy, the functions of ... Full text Link to item Cite

Regulation of mitochondrial antiviral signaling (MAVS) expression and signaling by the mitochondria-associated endoplasmic reticulum membrane (MAM) protein Gp78.

Journal Article J Biol Chem · January 17, 2014 In a previous study, we identified the E3 ubiquitin ligase Gp78 by RNAi high-throughput screening as a gene whose depletion restricted enterovirus infection. In the current study, we show that Gp78, which localizes to the ER-mitochondria interface, is a re ... Full text Link to item Cite

The role of trophoblastic microRNAs in placental viral infection.

Journal Article Int J Dev Biol · 2014 During the past decade, various types of small non-coding RNAs were found to be expressed in all kingdoms and phyla of life. Intense research efforts have begun to shed light on their biological functions, although much remains to be determined in order to ... Full text Link to item Cite

162: Unprecedented communication of microRNAs at the feto-maternal interface

Conference American Journal of Obstetrics and Gynecology · January 2014 Full text Cite

Mechanisms of MAVS regulation at the mitochondrial membrane.

Journal Article J Mol Biol · December 13, 2013 Mitochondria have emerged as critical platforms for antiviral innate immune signaling. This is due in large part to the mitochondrial localization of the innate immune signaling adaptor MAVS (mitochondrial antiviral signaling protein), which coordinates si ... Full text Link to item Cite

Autophagy as a mechanism of antiviral defense at the maternal-fetal interface.

Journal Article Autophagy · December 2013 Mechanisms to protect against viral infections are crucial during pregnancy as maternal-fetal transmission can have serious pathological outcomes, including fetal infection and its sequelae, such as growth restriction, birth defects, and/or fetal death. Th ... Full text Link to item Cite

Enter at your own risk: how enteroviruses navigate the dangerous world of pattern recognition receptor signaling.

Journal Article Cytokine · September 2013 Enteroviruses are the most common human viral pathogens worldwide. This genus of small, non-enveloped, single stranded RNA viruses includes coxsackievirus, rhinovirus, echovirus, and poliovirus species. Infection with these viruses can induce mild symptoms ... Full text Link to item Cite

Lipid raft- and SRC family kinase-dependent entry of coxsackievirus B into human placental trophoblasts.

Journal Article J Virol · August 2013 Maternal-fetal transmission of group B coxsackieviruses (CVB) during pregnancy has been associated with a number of diverse pathological outcomes, including hydrops fetalis, fetal myocarditis, meningoencephalitis, neurodevelopmental delays, congenital skin ... Full text Link to item Cite

Human placental trophoblasts confer viral resistance to recipient cells.

Journal Article Proc Natl Acad Sci U S A · July 16, 2013 Placental trophoblasts form the interface between the fetal and maternal environments and serve to limit the maternal-fetal spread of viruses. Here we show that cultured primary human placental trophoblasts are highly resistant to infection by a number of ... Full text Link to item Cite

Picornavirus entry.

Chapter · 2013 The essential event in picornavirus entry is the delivery of the RNA genome to the cytoplasm of a target cell, where replication occurs. In the past several years progress has been made in understanding the structural changes in the virion important for un ... Full text Link to item Cite

PAMPs and DAMPs: signal 0s that spur autophagy and immunity.

Journal Article Immunol Rev · September 2012 Pathogen-associated molecular pattern molecules (PAMPs) are derived from microorganisms and recognized by pattern recognition receptor (PRR)-bearing cells of the innate immune system as well as many epithelial cells. In contrast, damage-associated molecula ... Full text Open Access Link to item Cite

Focal adhesion kinase is a component of antiviral RIG-I-like receptor signaling.

Journal Article Cell Host Microbe · February 16, 2012 Viruses modulate the actin cytoskeleton at almost every step of their cellular journey from entry to egress. Cellular sensing of these cytoskeletal changes may function in the recognition of viral infection. Here we show that focal adhesion kinase (FAK), a ... Full text Link to item Cite

The actin cytoskeleton as a barrier to virus infection of polarized epithelial cells.

Journal Article Viruses · December 2011 Many diverse viruses target a polarized epithelial monolayer during host invasion. The polarized epithelium is adept at restricting the movement of solutes, ions, macromolecules, and pathogens across the mucosa. This regulation can be attributed to the pre ... Full text Open Access Link to item Cite

PKC alpha regulates Sendai virus-mediated interferon induction through HDAC6 and β-catenin.

Journal Article EMBO J · September 27, 2011 Recognition of viral RNA by cytoplasmic retinoic acid inducible gene I (RIG-I)-like receptors initiates signals leading to the induction of type I interferon (IFN) transcription via transcription factors such as interferon regulatory factor 3 (IRF3) and nu ... Full text Link to item Cite

Calcium signals and calpain-dependent necrosis are essential for release of coxsackievirus B from polarized intestinal epithelial cells.

Journal Article Mol Biol Cell · September 2011 Coxsackievirus B (CVB), a member of the enterovirus family, targets the polarized epithelial cells lining the intestinal tract early in infection. Although the polarized epithelium functions as a protective barrier, this barrier is likely exploited by CVB ... Full text Link to item Cite

Retinoic acid-induced gene-I (RIG-I) associates with nucleotide-binding oligomerization domain-2 (NOD2) to negatively regulate inflammatory signaling.

Journal Article J Biol Chem · August 12, 2011 Cytoplasmic caspase recruiting domain (CARD)-containing molecules often function in the induction of potent antimicrobial responses in order to protect mammalian cells from invading pathogens. Retinoic acid-induced gene-I (RIG-I) and nucleotide binding oli ... Full text Link to item Cite

The coxsackievirus B 3C protease cleaves MAVS and TRIF to attenuate host type I interferon and apoptotic signaling.

Journal Article PLoS Pathog · March 2011 The host innate immune response to viral infections often involves the activation of parallel pattern recognition receptor (PRR) pathways that converge on the induction of type I interferons (IFNs). Several viruses have evolved sophisticated mechanisms to ... Full text Link to item Cite

Comparative RNAi screening reveals host factors involved in enterovirus infection of polarized endothelial monolayers.

Journal Article Cell Host Microbe · January 20, 2011 Enteroviruses, including coxsackievirus B (CVB) and poliovirus (PV), can access the CNS through the blood brain barrier (BBB) endothelium to cause aseptic meningitis. To identify cellular components required for CVB and PV infection of human brain microvas ... Full text Link to item Cite

RNAi screening in mammalian cells to identify novel host cell molecules involved in the regulation of viral infections.

Journal Article Methods Mol Biol · 2011 It is clear that viral entry, replication, and spread is a complex process involving a dialog between the virus and the targeted host cell. Viruses have evolved highly specific strategies to hijack cellular factors to promote their internalization, initiat ... Full text Link to item Cite

Release of intracellular calcium stores facilitates coxsackievirus entry into polarized endothelial cells.

Journal Article PLoS Pathog · October 7, 2010 Group B coxsackieviruses (CVB) are associated with viral-induced heart disease and are among the leading causes of aseptic meningitis worldwide. Here we show that CVB entry into polarized brain microvasculature and aortic endothelial cells triggers a deple ... Full text Link to item Cite

Sar1 assembly regulates membrane constriction and ER export.

Journal Article J Cell Biol · July 12, 2010 The guanosine triphosphatase Sar1 controls the assembly and fission of COPII vesicles. Sar1 utilizes an amphipathic N-terminal helix as a wedge that inserts into outer membrane leaflets to induce vesicle neck constriction and control fission. We hypothesiz ... Full text Link to item Cite

A kinome RNAi screen identified AMPK as promoting poxvirus entry through the control of actin dynamics.

Journal Article PLoS Pathog · June 17, 2010 Poxviruses include medically important human pathogens, yet little is known about the specific cellular factors essential for their replication. To identify genes essential for poxvirus infection, we used high-throughput RNA interference to screen the Dros ... Full text Link to item Cite

Dynamin- and lipid raft-dependent entry of decay-accelerating factor (DAF)-binding and non-DAF-binding coxsackieviruses into nonpolarized cells.

Journal Article J Virol · November 2009 Group B coxsackieviruses (CVB) use the CVB and adenovirus receptor (CAR) to enter and infect cells. Some CVB also bind to decay-accelerating factor (DAF), but that interaction alone is insufficient for infection. We previously found that CVB3 entry into po ... Full text Link to item Cite

Retinoic acid-induced gene-1 (RIG-I) associates with the actin cytoskeleton via caspase activation and recruitment domain-dependent interactions.

Journal Article J Biol Chem · March 6, 2009 The actin cytoskeleton serves as a barrier that protects mammalian cells from environmental pathogens such as bacteria, fungi, and viruses. Several components of antimicrobial signaling pathways have been shown to associate directly with the actin cytoskel ... Full text Link to item Cite

Tight junction proteins claudin-1 and occludin control hepatitis C virus entry and are downregulated during infection to prevent superinfection.

Journal Article J Virol · February 2009 A tight junction (TJ) protein, claudin-1 (CLDN1), was identified recently as a key factor for hepatitis C virus (HCV) entry. Here, we show that another TJ protein, occludin, is also required for HCV entry. Mutational study of CLDN1 revealed that its tight ... Full text Link to item Cite

The distinct roles of JAM-A in reovirus pathogenesis.

Journal Article Cell Host Microbe · January 22, 2009 Despite their fundamental role in host defense, many components of epithelial and endothelial tight junctions serve as viral receptors. In this issue of Cell Host & Microbe, Antar et al. (2009) provide striking in vivo evidence that the broadly expressed r ... Full text Link to item Cite

Correlation of the tight junction-like distribution of Claudin-1 to the cellular tropism of hepatitis C virus.

Journal Article J Biol Chem · March 28, 2008 Claudin-1 (CLDN1), a tight junction (TJ) protein, has recently been identified as an entry co-receptor for hepatitis C virus (HCV). Ectopic expression of CLDN1 rendered several non-hepatic cell lines permissive to HCV infection. However, little is known ab ... Full text Link to item Cite

Coxsackievirus entry across epithelial tight junctions requires occludin and the small GTPases Rab34 and Rab5.

Journal Article Cell Host Microbe · September 13, 2007 The major group B coxsackievirus (CVB) receptor is a component of the epithelial tight junction (TJ), a protein complex that regulates the selective passage of ions and molecules across the epithelium. CVB enters polarized epithelial cells from the TJ, cau ... Full text Link to item Cite

Poliovirus entry into human brain microvascular cells requires receptor-induced activation of SHP-2.

Journal Article EMBO J · September 5, 2007 Viruses use specific receptor molecules to bind selectively to target cells. Receptors have often been considered as mere docking sites, but they may also possess intrinsic signaling capacities that serve to prime the cell for entry and infection. Poliovir ... Full text Link to item Cite