scholarly journals A role for dual viral hits in causation of subacute sclerosing panencephalitis

2005 ◽  
Vol 202 (9) ◽  
pp. 1185-1190 ◽  
Author(s):  
Michael B.A. Oldstone ◽  
Samuel Dales ◽  
Antoinette Tishon ◽  
Hanna Lewicki ◽  
Lee Martin
Keyword(s):  
Measles Virus ◽  
B Lymphocyte ◽  
Subacute Sclerosing Panencephalitis ◽  
Small Animal ◽  
Transgenic Mouse Model ◽  
Lymphocytic Choriomeningitis ◽  
Small Animal Model ◽  
M Gene ◽  
The Matrix ◽  
The Central Nervous System

Subacute sclerosing panencephalitis (SSPE) is a progressive fatal neurodegenerative disease associated with persistent infection of the central nervous system (CNS) by measles virus (MV), biased hypermutations of the viral genome affecting primarily the matrix (M) gene with the conversion of U to C and A to G bases, high titers of antibodies to MV, and infiltration of B cells and T cells into the CNS. Neither the precipitating event nor biology underlying the MV infection is understood, nor is their any satisfactory treatment. We report the creation of a transgenic mouse model that mimics the cardinal features of SSPE. This was achieved by initially infecting mice expressing the MV receptor with lymphocytic choriomeningitis virus Cl 13, a virus that transiently suppressed their immune system. Infection by MV 10 days later resulted in persistent MV infection of neurons. Analysis of brains from infected mice showed the biased U to C hypermutations in the MV M gene and T and B lymphocyte infiltration. These sera contained high titers of antibodies to MV. Thus, a small animal model is now available to both molecularly probe the pathogenesis of SSPE and to test a variety of therapies to treat the disease.

scholarly journals Increased positive selection pressure in persistent (SSPE) versus acute measles virus infections

2002 ◽  
Vol 83 (6) ◽  
pp. 1419-1430 ◽  
Author(s):  
Christopher H. Woelk ◽  
Oliver G. Pybus ◽  
Li Jin ◽  
David W. G. Brown ◽  
Edward C. Holmes
Keyword(s):  
Positive Selection ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Surface Glycoprotein ◽  
Virus Infections ◽  
M Gene ◽  
Positive Selection Pressure ◽  
Functional Studies ◽  
The Matrix ◽  
Gene Data

We compared the extent of positive selection acting on acute and persistent strains of measles virus (MV). Far stronger positive selection was found in the fusion (F) and haemagglutinin (H) genes from subacute sclerosing panencephalitis (SSPE) compared to acute MV cases. Most of the positively selected sites identified in these surface glycoprotein genes from SSPE cases correspond to structural, functional or antigenic areas, and could not be explained by the effects of cell passaging. The correlations between selected sites and functional studies of MV are discussed in detail with reference to the maintenance of persistent infection. No positive selection was found in the matrix (M) gene from acute cases of MV and the effects of including hypermutated SSPE M gene sequences in phylogenetic inference were also explored. Finally, using H gene data, we estimated the rate of molecular evolution for SSPE strains as 3·4×10−4 substitutions/site/year, which is similar to previous estimates obtained for acute strains.

Presence of antibody in virus-infected brain cells of SSPE ferrets

1983 ◽  
Vol 41 ◽  
pp. 804-805
Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar
Keyword(s):  
Measles Virus ◽  
Plasma Cells ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Brain Cells ◽  
Antibody Titers ◽  
A Cell ◽  
The Central Nervous System ◽  
The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

scholarly journals 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

2014 ◽  
Vol 89 (5) ◽  
pp. 2710-2717 ◽  
Author(s):  
Shumpei Watanabe ◽  
Shinji Ohno ◽  
Yuta Shirogane ◽  
Satoshi O. Suzuki ◽  
Ritsuko Koga ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Fusion Protein ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Neuronal Cells ◽  
Extracellular Domain ◽  
Fusion Activity ◽  
F Protein ◽  
The Central Nervous System

ABSTRACTSubacute 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.IMPORTANCESubacute 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.

scholarly journals A mouse model of persistent brain infection with recombinant Measles virus

2006 ◽  
Vol 87 (7) ◽  
pp. 2011-2019 ◽  
Author(s):  
S. Schubert ◽  
K. Möller-Ehrlich ◽  
K. Singethan ◽  
S. Wiese ◽  
W. P. Duprex ◽  
...  
Keyword(s):  
Immune System ◽  
Measles Virus ◽  
Fluorescent Protein ◽  
Subacute Sclerosing Panencephalitis ◽  
Cns Infection ◽  
Brain Infection ◽  
The Central Nervous System ◽  
Immunocompetent Mice ◽  
Green Fluorescent ◽  
Histological Staining

Measles virus (MV) nucleocapsids are present abundantly in brain cells of patients with subacute sclerosing panencephalitis (SSPE). This invariably lethal brain disease develops years after acute measles as result of a persistent MV infection. Various rodent models for MV infection of the central nervous system (CNS) have been described in the past, in which the detection of viral antigens is based on histological staining procedures of paraffin embedded brains. Here, the usage of a recombinant MV (MV-EGFP-CAMH) expressing the haemagglutinin (H) of the rodent-adapted MV-strain CAM/RB and the enhanced green fluorescent protein (EGFP) is described. In newborn rodents the virus infects neurons and causes an acute lethal encephalitis. From 2 weeks on, when the immune system of the genetically unmodified animal is maturating, intracerebral (i.c.) infection is overcome subclinically, however, a focal persistent infection in groups of neurons remains. The complete brain can be analysed in 50 or 100 μm slices, and infected autofluorescent cells are readily detected. Seven and 28 days post-infection (p.i.) 86 and 81 % of mice are infected, respectively, and virus persists for more than 50 days p.i. Intraperitoneal immunization with MV 1 week before infection, but not after infection, protects and prevents persistence. The high percentage of persistence demonstrates that this is a reliable and useful model of a persistent CNS infection in fully immunocompetent mice, which allows the investigation of determinants of the immune system.

scholarly journals Adult Onset Subacute Sclerosing Panencephalitis: A case report

2017 ◽  
Vol 2 (1) ◽  
pp. 40-42
Author(s):  
Mohammad Akter Hossain ◽  
Romal Chowdhury ◽  
Nazmul Islam ◽  
Md Azharul Hoque ◽  
Md Enayet Hussain
Keyword(s):  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Accurate Diagnosis ◽  
Adult Onset ◽  
Chronic Encephalitis ◽  
The Central Nervous System ◽  
Atypical Feature ◽  
High Index Of Suspicion ◽  
Electroencephalogram Eeg ◽  
Young Adolescence

Subacute sclerosing panencephalitis (SSPE) is a chronic encephalitis of childhood and young adolescence due to persistent measles virus infection of the central nervous system (CNS). In majority of cases, onset occurs between 5-10 years of age. SSPE generally occurs 5-10 years after measles virus infection1. The diagnosis of SSPE is based on characteristic clinical and electroencephalogram (EEG) findings, increase measles antibody titer in cerebrospinal fluid (CSF) and serum. As onset of SSPE in adults is rare and may have atypical feature it requires high index of suspicion for early and accurate diagnosis. Herein, we report a case of SSPE in a male of 26 years with recurrent episodes of myoclonic jerks. Journal of National Institute of Neurosciences Bangladesh, 2016;2(1): 40-42

Acute Measles Encephalitis in Children With Immunosuppression

PEDIATRICS ◽  
1977 ◽  
Vol 59 (2) ◽  
pp. 232-239
Author(s):  
Jean Aicardi ◽  
Francoise Goutieres ◽  
Maria-Leonor Arsenio-Nunes ◽  
Pierre Lebon
Keyword(s):  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Immunosuppressive Drugs ◽  
Prominent Feature ◽  
Epilepsia Partialis Continua ◽  
Fatal Course ◽  
Immunosuppressed Patients ◽  
History Of ◽  
The Central Nervous System ◽  
The Brain

Four cases of encephalitis occurring in children treated for lymphatic malignancies by immunosuppressive drugs are reported. Measles virus was isolated from the brain in one case and identified immunologically in another. Nucleocapsids identical to those seen in subacute sclerosing panencephalitis were demonstrated in three cases. Severe immunosuppression was evidenced in two patients by failure of rosette formation and low phytohemagglutinin tests. Pathologically, the inflammatory reaction was absent in one brain and moderate in two. Clinically, epilepsia partialis continua was a prominent feature in three patients. A history of measles or of contact was elicited in three cases, five weeks to three months before onset. All cases ran an acute fatal course. Measles virus can behave as an opportunistic invader of the central nervous system in children and the diagnosis of measles encephalitis should be considered in immunosuppressed patients.

scholarly journals Characterization of a new genotype of measles virus detected in China and England

1998 ◽  
Vol 121 (3) ◽  
pp. 691-697 ◽  
Author(s):  
L. JIN ◽  
Y. J. SUN ◽  
L. GE ◽  
D. W. G. BROWN
Keyword(s):  
Measles Virus ◽  
Direct Sequencing ◽  
N Gene ◽  
M Gene ◽  
New Genotype ◽  
H Gene ◽  
The Matrix ◽  
The Usa ◽  
The Uk ◽  
Nucleoprotein N

We report the co-circulation of a new lineage of measles virus (MV) and an Edmonston-like (Ed-like) genotype of MV in China during 1995–7. Sequence analysis of 25 strains was performed on a 282 nucleotides (nt) region of the nucleoprotein (N) gene, a 450-nt region of the haemagglutinin (H) gene and a 152-nt region of the matrix (M) gene by direct sequencing of RT-PCR amplicons obtained from clinical specimens. The entire H gene was sequenced from two strains. The results showed that 24/25 Chinese strains belonged to a new genogroup and were distinct from the vaccine strains used in China and the UK, and also from MV strains previously described in Europe, Africa and the USA. The remaining strain was Ed-like. Two strains of the new genotype (IV) and one of the Ed-like genotype were also detected in the UK in 1996.

scholarly journals Atypical subacute sclerosing panencephalitis: case report

2007 ◽  
Vol 65 (4a) ◽  
pp. 1030-1033 ◽  
Author(s):  
Marcelo Maroco Cruzeiro ◽  
Thiago Cardoso Vale ◽  
Leopoldo Antônio Pires ◽  
Gláucio Mendes Franco
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Case Report ◽  
Virus Infection ◽  
Effective Treatment ◽  
Measles Virus ◽  
Poor Prognosis ◽  
Subacute Sclerosing Panencephalitis ◽  
Inflammatory Disorder ◽  
The Central Nervous System

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.

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