Use of Protein a Conjugated to Peroxidase to Localize Immunoglobulin G in SSPE Ferret Brain

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.


2009 ◽  
Vol 200 (7) ◽  
pp. 1031-1038 ◽  
Author(s):  
Nitya Nair ◽  
William J. Moss ◽  
Susana Scott ◽  
Nanthalile Mugala ◽  
Zaza M. Ndhlovu ◽  
...  

2004 ◽  
Vol 11 (3) ◽  
pp. 615-617 ◽  
Author(s):  
Alyson J. Littman ◽  
Lisa A. Jackson ◽  
Emily White ◽  
Mark D. Thornquist ◽  
Charlotte A. Gaydos ◽  
...  

ABSTRACT To evaluate the reliability of Chlamydia pneumoniae-specific immunoglobulin G (IgG) and IgA antibody titers as measured by the microimmunofluorescence (MIF) test, we compared results from 392 individuals using a standard MIF protocol at two academic laboratories. The kappas for dichotomous titers (≥16 versus <16) were 0.39 for IgA and 0.53 for IgG. Measurement error likely attenuates C. pneumoniae-disease associations; the magnitude of attenuation can be estimated from results of studies such as this one.


2019 ◽  
Vol 94 (2) ◽  
Author(s):  
Yuta Shirogane ◽  
Takao Hashiguchi ◽  
Yusuke Yanagi

ABSTRACT Measles virus (MeV) is an enveloped RNA virus bearing two envelope glycoproteins, the hemagglutinin (H) and fusion (F) proteins. Upon receptor binding, the H protein triggers conformational changes of the F protein, causing membrane fusion and subsequent virus entry. MeV may persist in the brain, infecting neurons and causing fatal subacute sclerosing panencephalitis (SSPE). Since neurons do not express either of the MeV receptors, signaling lymphocytic activation molecule (SLAM; also called CD150) and nectin-4, how MeV propagates in neurons is unknown. Recent studies have shown that specific substitutions in the F protein found in MeV isolates from SSPE patients are critical for MeV neuropathogenicity by rendering the protein unstable and hyperfusogenic. Recombinant MeVs possessing the F proteins with such substitutions can spread in primary human neurons and in the brains of mice and hamsters and induce cell-cell fusion in cells lacking SLAM and nectin-4. Here, we show that receptor-blind mutant H proteins that have decreased binding affinities to receptors can support membrane fusion mediated by hyperfusogenic mutant F proteins, but not the wild-type F protein, in cells expressing the corresponding receptors. The results suggest that weak interactions of the H protein with certain molecules (putative neuron receptors) trigger hyperfusogenic F proteins in SSPE patients. Notably, where cell-cell contacts are ensured, the weak cis interaction of the H protein with SLAM on the same cell surface also could trigger hyperfusogenic F proteins. Some enveloped viruses may exploit such cis interactions with receptors to infect target cells, especially in cell-to-cell transmission. IMPORTANCE Measles virus (MeV) may persist in the brain, causing incurable subacute sclerosing panencephalitis (SSPE). Because neurons, the main target in SSPE, do not express receptors for wild-type (WT) MeV, how MeV propagates in the brain is a key question for the disease. Recent studies have demonstrated that specific substitutions in the MeV fusion (F) protein are critical for neuropathogenicity. Here, we show that weak cis and trans interactions of the MeV attachment protein with receptors that are not sufficient to trigger the WT MeV F protein can trigger the mutant F proteins from neuropathogenic MeV isolates. Our study not only provides an important clue to understand MeV neuropathogenicity but also reveals a novel viral strategy to expand cell tropism.


2017 ◽  
Vol 16 (01) ◽  
pp. 021-024
Author(s):  
Aniruddha More ◽  
Rajesh Verma

AbstractSubacute sclerosing panencephalitis (SSPE) is a potentially fatal progressive complication of measles virus infection of the brain occurring in children and adolescents. It typically presents with a progressive decline in cognitive abilities along with periodic myoclonic jerks. We report a case of SSPE with atypical presentation. Our patient presented with intermittent drop attacks without any obvious myoclonic jerks or cognitive decline making his diagnosis difficult. Atypical manifestations of SSPE occur in 10% of patients, and a high index of suspicion is necessary for early diagnosis and management of this dreaded disease.


Cytokine ◽  
2011 ◽  
Vol 56 (3) ◽  
pp. 676-679 ◽  
Author(s):  
Shunji Hasegawa ◽  
Natsumi Mori ◽  
Mika Satomi ◽  
Da-Peng Jiang ◽  
Hak Hotta ◽  
...  

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