Nonpolio Enterovirus Infections in Neonates

Haston, Julia C.; Dixon, Terry C.

doi:10.3928/00904481-20150512-09

Cited by 18 publications

(12 citation statements)

References 28 publications

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“…Compared to other common viral pathogens such as herpes simplex virus and Japanese encephalitis virus, EV-induced meningoencephalitis is generally mild, with moderate lymphocytic pleocytosis in CSF. 2,12,43 This provides a unique opportunity to query the direct impact of viral infection without severe confounding influences that dwarf the subtle changes prelude to substantial neurologic manifestation.…”

Section: ■ Discussionmentioning

confidence: 99%

Proteomic Analysis of Cerebrospinal Fluid in Children with Acute Enterovirus-Associated Meningoencephalitis Identifies Dysregulated Host Processes and Potential Biomarkers

Sun

et al. 2020

J. Proteome Res.

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Enteroviruses (EVs) are major causes of viral meningoencephalitis in children. To better understand the pathogenesis and identify potential biomarkers, cerebrospinal fluid proteome in children (n = 52) suffering from EV meningoencephalitis was compared to that in EV-negative control subjects (n = 53) using the BoxCar acquisition technique. Among 1697 proteins identified, 1193 with robust assay readouts were used for quantitative analyses. Differential expression analyses identified 154 upregulated and 227 downregulated proteins in the EV-positive group. Functional analyses showed that the upregulated proteins are mainly related to activities of lymphocytes and cytokines, inflammation, and responses to stress and viral invasion, while the downregulated proteins are mainly related to neuronal integrity and activity as well as neurogenesis. According to receiver operating characteristic analysis results, Rho-GDP-dissociation inhibitor 2 exhibited the highest sensitivity (96.2%) and specificity (100%) for discriminating EV-positive from EV-negative patients. The chemokine CXCL10 was most upregulated (>300-fold) with also high sensitivity (92.3%) and specificity (94.3%) for indicating EV positivity. Thus, this study uncovered perturbations of multiple host processes due to EV meningoencephalitis, especially the general trend of enhanced immune responses but impaired neuronal functions. The identified dysregulated proteins may also prompt biomarker development.

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Section: ■ Discussionmentioning

confidence: 99%

Proteomic Analysis of Cerebrospinal Fluid in Children with Acute Enterovirus-Associated Meningoencephalitis Identifies Dysregulated Host Processes and Potential Biomarkers

Sun

et al. 2020

J. Proteome Res.

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“…Echoviruses are common causes of aseptic meningitis worldwide, and also of severe hepatitis, neurological disease, and death in neonates and infants. 70,71 Echovirus particles attach to the host cell surface by directly binding FcRn (Fig 4), a receptor both necessary and sufficient for echovirus infection. 4,72 FcRn is expressed in sites often affected by echovirus infection, such as the placenta, intestinal enterocytes, liver hepatocytes, and endothelial cells that line the blood-brain barrier.…”

Section: Fcrn As An Echovirus Receptormentioning

confidence: 99%

Neonatal Fc receptor in human immunity: Function and role in therapeutic intervention

Patel

Bussel

2020

Journal of Allergy and Clinical Immunology

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The humoral immune response provides specific, long-lived protection against invading pathogens, via immunoglobulin production and other memory functions. IgG, the most abundant immunoglobulin isotype, has the longest half-life and protects against bacterial and viral infections. The neonatal Fc receptor (FcRn) transports IgG across barriers, for example, the placenta, enhancing fetal humoral immunity to levels similar to their mothers'. Importantly, FcRn, by protecting IgG from intracellular degradation, results in an approximately 21-day circulating IgG half-life and high plasma levels; similarly, FcRn recycles albumin and is the portal of entry for enteric cytopathic human orphan (echo) virus infection. Dysregulated immune responses may lead to antibodies against self-antigens (autoantibodies), resulting in organ-specific or systemic autoimmune diseases. Autoantibody-mediated diseases have been treated by nonspecific immunoglobulin-lowering/ modulating therapies, including immunoadsorption, plasma exchange, and high-dose intravenous immunoglobulin. However, targeting FcRn with specific inhibitors results in reduction in only IgG levels. The effectiveness of FcRn inhibitors in autoimmune diseases, including myasthenia gravis and immune thrombocytopenia, provides further evidence that IgG is a primary driver in these autoantibody-mediated diseases. We describe the role of FcRn in human biology, including insights that clinical testing of FcRn inhibitors have provided into FcRn biology and autoimmune disease mechanisms, allowing fact-based speculation on their therapeutic potential.

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“…Enteroviruses are the main causative agents of aseptic meningitis worldwide, with echovirus 9 (E9) and echovirus 30 (E30) amongst the most commonly circulating serotypes (1). The neonatal and infant populations are at greatest risk for developing severe echovirus-induced disease and infection within the first few weeks of life can be fatal (2, 3). Enteroviral infections are also devastating in Neonatal Intensive Care Units (NICUs), where they account for 15-30% of NICU-associated nosocomial viral infections and result in death of the neonate in as many as 25% of cases (4–7), the majority of which result from echovirus 11 (E11) infections (8).…”

Section: Introductionmentioning

confidence: 99%

The neonatal Fc receptor is a pan-echovirus receptor

Morosky

Evans

Lemon

et al. 2018

Preprint

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52Echoviruses are the main causative agents of aseptic meningitis worldwide and are particularly 53 devastating in the neonatal population, where they are associated with severe hepatitis, 54 neurological disease including meningitis and encephalitis, and even death. Here, we identify the 55 neonatal Fc receptor (FcRn) as a pan-echovirus receptor. We show that loss of expression of 56 FcRn or its binding partner beta 2 microglubulin (b2M) renders human brain microvascular cells 57 resistant to infection by a panel of echoviruses at the stage of virus attachment and that a blocking 58 antibody to b2M inhibit echovirus infection in cell lines and in primary human fetal intestinal 59 epithelial cells. We also show that expression of human, but not mouse, FcRn renders non-60 permissive human and mouse cells sensitive to echovirus infection and that the extracellular 61 domain of human FcRn directly binds echoviral particles and neutralizes infection. Lastly, we 62 show that primary cells isolated from mice that express human FcRn are highly susceptible to 63 echovirus infection. Our findings thus identify FcRn as a pan-echovirus receptor, which may 64 explain the enhanced susceptibility of neonates to echovirus infections. 65 66 Significance 67 68 Echoviruses are associated with aseptic meningitis and induce severe disease, and even death, 69 in neonates and young infants. Here, we identify the neonatal Fc receptor (FcRn) as a pan-70 echovirus receptor. FcRn is expressed on the surface of the human placenta, and throughout life 71 in intestinal enterocytes, liver hepatocytes, and in the microvascular endothelial cells that line the 72 blood-brain barrier. This pattern of expression is consistent with the organ sites targeted by 73 echoviruses in humans, with the primary entry site of infection in the intestinal tract and 74

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Nonpolio Enterovirus Infections in Neonates

Cited by 18 publications

References 28 publications

Proteomic Analysis of Cerebrospinal Fluid in Children with Acute Enterovirus-Associated Meningoencephalitis Identifies Dysregulated Host Processes and Potential Biomarkers

Proteomic Analysis of Cerebrospinal Fluid in Children with Acute Enterovirus-Associated Meningoencephalitis Identifies Dysregulated Host Processes and Potential Biomarkers

Neonatal Fc receptor in human immunity: Function and role in therapeutic intervention

The neonatal Fc receptor is a pan-echovirus receptor

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