scholarly journals Generalized and localized biased hypermutation affecting the matrix gene of a measles virus strain that causes subacute sclerosing panencephalitis.

1989 ◽  
Vol 63 (12) ◽  
pp. 5464-5468 ◽  
Author(s):  
T C Wong ◽  
M Ayata ◽  
A Hirano ◽  
Y Yoshikawa ◽  
H Tsuruoka ◽  
...  
2005 ◽  
Vol 202 (9) ◽  
pp. 1185-1190 ◽  
Author(s):  
Michael B.A. Oldstone ◽  
Samuel Dales ◽  
Antoinette Tishon ◽  
Hanna Lewicki ◽  
Lee Martin

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.


1990 ◽  
Vol 18 (17) ◽  
pp. 5283-5283 ◽  
Author(s):  
Robin Buckland ◽  
Valérie Cheynet ◽  
Philippe Beauverger ◽  
Fabian Wild
Keyword(s):  

2013 ◽  
Vol 17 ◽  
pp. 71-78 ◽  
Author(s):  
Jelena Ivancic-Jelecki ◽  
Marijana Baricevic ◽  
Maja Šantak ◽  
Matija Harcet ◽  
Goran Tešović ◽  
...  

2002 ◽  
Vol 83 (6) ◽  
pp. 1419-1430 ◽  
Author(s):  
Christopher H. Woelk ◽  
Oliver G. Pybus ◽  
Li Jin ◽  
David W. G. Brown ◽  
Edward C. Holmes

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.


Author(s):  
Hannah R. Brown ◽  
Anthony F. Nostro ◽  
Halldor Thormar

Subacute sclerosing panencephalitis (SSPE) is a slowly progressing disease of the CNS in children which is caused by measles virus. Ferrets immunized with measles virus prior to inoculation with the cell associated, syncytiogenic D.R. strain of SSPE virus exhibit characteristics very similar to the human disease. Measles virus nucleocapsids are present, high measles antibody titers are found in the sera and inflammatory lesions are prominent in the brains. Measles virus specific immunoglobulin G (IgG) is present in the brain,and IgG/ albumin ratios indicate that the antibodies are synthesized within the CNS.


Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar

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.


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