Congenital echovirus 21 infection causing fulminant hepatitis in a neonate

Pedrosa, Cristina; Lage, Maria João; Virella, Daniel

doi:10.1136/bcr-2012-008394

Cited by 12 publications

(5 citation statements)

References 11 publications

(16 reference statements)

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“…In addition, our studies suggest that echovirus infection of hepatocytes induces pronounced hepatic damage, characterized by apoptotic cell death and tissue damage. These findings are consistent with what is observed in autopsy tissue isolated from echovirus infected neonates, which also indicates extensive infection-induced hepatocyte damage 23,35,38,39 .…”

Section: Despite the Clear Hepatic Tropism Of Echoviruses Little Is supporting

confidence: 90%

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

Wells

Grimes

Kim

et al. 2020

Preprint

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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 ablation of type I interferon (IFN) signaling are key host determinants involved in echovirus pathogenesis. We show that expression of hFcRn alone is insufficient to confer susceptibility to echovirus infections in mice. However, expression of hFcRn in mice deficient in type I interferon (IFN) signaling, hFcRn-IFNAR−/−, recapitulate the echovirus pathogenesis observed in humans. Luminex-based multianalyte profiling from E11 infected hFcRn-IFNAR−/− mice revealed a robust systemic immune response to infection, including the induction of type I IFNs. Furthermore, similar to the severe hepatitis observed in humans, E11 infection in hFcRn-IFNAR−/− mice caused profound liver damage. Our findings define the host factors involved in echovirus pathogenesis and establish in vivo models that recapitulate echovirus disease.

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Section: Despite the Clear Hepatic Tropism Of Echoviruses Little Is supporting

confidence: 90%

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

Wells

Grimes

Kim

et al. 2020

Preprint

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“…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). In neonates, vertical transmission may occur at the time of delivery following a maternal infection in the days or weeks prior to delivery (9). In addition, echovirus infections have also been observed in utero, both at late and earlier stages of pregnancy, where they are associated with fetal death (10–14).…”

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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“…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). In neonates, vertical transmission may occur before or at the time of delivery following a maternal infection (4). Echovirus infections in utero, both at late and earlier stages of pregnancy, have also been associated with fetal death (5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

The neonatal Fc receptor is a pan-echovirus receptor

Morosky

Wells

Lemon

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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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 encephalitis, and even death. Here, we identify the neonatal Fc receptor (FcRn) as a pan-echovirus receptor. We show that loss of expression of FcRn or its binding partner beta 2 microglobulin (β2M) renders cells resistant to infection by a panel of echoviruses at the stage of virus attachment, and that a blocking antibody to β2M inhibits echovirus infection in cell lines and in primary human intestinal epithelial cells. We also show that expression of human, but not mouse, FcRn renders nonpermissive human and mouse cells sensitive to echovirus infection and that the extracellular domain of human FcRn directly binds echovirus particles and neutralizes infection. Lastly, we show that neonatal mice expressing human FcRn are more susceptible to echovirus infection by the enteral route. Our findings thus identify FcRn as a pan-echovirus receptor, which may explain the enhanced susceptibility of neonates to echovirus infections.

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Congenital echovirus 21 infection causing fulminant hepatitis in a neonate

Cited by 12 publications

References 11 publications

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

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

The neonatal Fc receptor is a pan-echovirus receptor

The neonatal Fc receptor is a pan-echovirus receptor

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