Subacute Sclerosing Panencephalitis: More Cases of This Fatal Disease Are Prevented by Measles Immunization than Was Previously Recognized

Bellini, William J.; Rota, Jennifer S.; Lowe, Luis; Katz, Russell S.; Dyken, Paul R.; Zaki, Sherif R.; Shieh, Wun‐Ju; Rota, Paul A.

doi:10.1086/497169

Cited by 208 publications

(124 citation statements)

References 48 publications

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“…The typical clinical picture of measles may have been altered by the presence of maternal antibodies. It has also been speculated that the infection in this circumstance may be due to infection by a wild strain which is not included in the vaccine used 12 . There is no evidence to suggest that the attenuated vaccine virus is responsible for sporadic cases of SSPE 8 .…”

Section: Discussionmentioning

confidence: 99%

Atypical subacute sclerosing panencephalitis: case report

Cruzeiro

Vale

Pires

et al. 2007

Arq. Neuro-Psiquiatr.

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-Subacute sclerosing panencephalitis (SSPE) is a progressive inflammatory disorder of the central nervous system with both poor prognosis and high mortality. The disease has been related to a persistent and aberrant measles virus infection and no effective treatment has been available. We report a case of SSPE with atypical features including seizures at onset and a fulminant course in a 8 years-old boy who had been previously immunized against measles.KEY WORDS: subacute sclerosing panencephalitis, measles, immunization.Panencefalite esclerosante subaguda: relato de caso atípico RESUMO -Panencefalite esclerosante subaguda (PES) é uma doença inflamatória e progressiva do sistema nervoso central com prognóstico reservado e alta mortalidade. A doença tem sido relacionada com a infecção persistente e anormal pelo vírus do sarampo e não há tratamento específico disponível. Relatamos um caso de PES com características atípicas representadas por início do quadro com crises convulsivas e apresentação fulminante em menino de 8 anos previamente imunizado contra o vírus do sarampo.PALAVRAS-CHAVE: panencefalite esclerosante subaguda, sarampo, imunização.

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Section: Discussionmentioning

confidence: 99%

Atypical subacute sclerosing panencephalitis: case report

Cruzeiro

Vale

Pires

et al. 2007

Arq. Neuro-Psiquiatr.

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“…In addition to these authentic receptors, vaccine and laboratory-adapted strains of MV can use CD46, a complement regulatory molecule, as an alternative receptor (13-15), through specific amino acid changes in its receptor-binding protein hemagglutinin (H) (16,17). Furthermore, MV sometimes persists in the central nervous system (CNS) and causes a fatal degenerative disease, subacute sclerosing panencephalitis (SSPE), several years after acute measles (1,(18)(19)(20). In SSPE, MV appears to infect neuronal cells independently of SLAM and nectin 4, since neither SLAM nor nectin 4 is expressed at significant levels in the human CNS (21-23).…”

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confidence: 99%

Measles Virus Mutants Possessing the Fusion Protein with Enhanced Fusion Activity Spread Effectively in Neuronal Cells, but Not in Other Cells, without Causing Strong Cytopathology

Watanabe

Ohno

Shirogane

et al. 2015

J Virol

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Subacute sclerosing panencephalitis (SSPE) is caused by persistent measles virus (MV) infection in the central nervous system (CNS). Since human neurons, its main target cells, do not express known MV receptors (signaling lymphocyte activation molecule [SLAM] and nectin 4), it remains to be understood how MV infects and spreads in them. We have recently reported that fusion-enhancing substitutions in the extracellular domain of the MV fusion (F) protein (T461I and S103I/N462S/N465S), which are found in multiple SSPE virus isolates, promote MV spread in human neuroblastoma cell lines and brains of suckling hamsters. In this study, we show that hyperfusogenic viruses with these substitutions also spread efficiently in human primary neuron cultures without inducing syncytia. These substitutions were found to destabilize the prefusion conformation of the F protein trimer, thereby enhancing fusion activity. However, these hyperfusogenic viruses exhibited stronger cytopathology and produced lower titers at later time points in SLAM-or nectin 4-expressing cells compared to the wild-type MV. Although these viruses spread efficiently in the brains of SLAM knock-in mice, they did not in the spleens. Taken together, the results suggest that enhanced fusion activity is beneficial for MV to spread in neuronal cells where no cytopathology occurs, but detrimental to other types of cells due to strong cytopathology. Acquisition of enhanced fusion activity through substitutions in the extracellular domain of the F protein may be crucial for MV's extensive spread in the CNS and development of SSPE. IMPORTANCE Subacute sclerosing panencephalitis (SSPE) is a fatal disease caused by persistent measles virus (MV) infection in the central nervous system (CNS).Its cause is not well understood, and no effective therapy is currently available. Recently, we have reported that enhanced fusion activity of MV through the mutations in its fusion protein is a major determinant of efficient virus spread in human neuronal cells and brains of suckling hamsters. In this study, we show that those mutations render the conformation of the fusion protein less stable, thereby making it hyperfusogenic. Our results also show that enhanced fusion activity is beneficial for MV to spread in the CNS but detrimental to other types of cells in peripheral tissues, which are strongly damaged by the virus. Our findings provide important insight into the mechanism for the development of SSPE after MV infection. M easles is a highly contagious disease characterized by high fever, cough, and maculopapular rash (1). The causative agent, measles virus (MV), is thought to first infect alveolar macrophages and dendritic cells of the respiratory tract, which transport the virus to local lymph nodes, where it replicates efficiently (2, 3). This allows MV to spread to other lymphoid organs throughout the body via the bloodstream, followed by infection of respiratory epithelia at later stages. Progeny viral particles are then shed from the epithelial cells through ...

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“…Although MV also exhibits neurovirulence and causes a persistent infection of the CNS, subacute sclerosing panencephalitis (SSPE), neither SLAM nor nectin4 was detected in neural cells of the human CNS (13,14,20). The frequency of SSPE is 1/5,000 to 1/100,000 in reported cases of acute measles (3,19). In contrast, acute infection of animals with CDV is often accompanied by severe neurological manifestations, which are rarely seen in patients with acute measles (2,21).…”

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confidence: 99%

Nectin4 Is an Epithelial Cell Receptor for Canine Distemper Virus and Involved in Neurovirulence

Pratakpiriya

Seki

Otsuki

et al. 2012

J Virol

117

105

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Canine distemper virus (CDV) uses signaling lymphocyte activation molecule (SLAM), expressed on immune cells, as a receptor. However, epithelial and neural cells are also affected by CDVin vivo. Wild-type CDV strains showed efficient replication with syncytia in Vero cells expressing dog nectin4, and the infection was blocked by an anti-nectin4 antibody. In dogs with distemper, CDV antigen was preferentially detected in nectin4-positive neurons and epithelial cells, suggesting that nectin4 is an epithelial cell receptor for CDV and also involved in its neurovirulence.

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Subacute Sclerosing Panencephalitis: More Cases of This Fatal Disease Are Prevented by Measles Immunization than Was Previously Recognized

Cited by 208 publications

References 48 publications

Atypical subacute sclerosing panencephalitis: case report

Atypical subacute sclerosing panencephalitis: case report

Measles Virus Mutants Possessing the Fusion Protein with Enhanced Fusion Activity Spread Effectively in Neuronal Cells, but Not in Other Cells, without Causing Strong Cytopathology

Nectin4 Is an Epithelial Cell Receptor for Canine Distemper Virus and Involved in Neurovirulence

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