scholarly journals Comparison of wild-type and subacute sclerosing panencephalitis strains of measles virus. Neurovirulence in ferrets and biological properties in cell cultures.

1978 ◽  
Vol 148 (3) ◽  
pp. 674-691 ◽  
Author(s):  
H Thormar ◽  
P D Mehta ◽  
H R Brown
Keyword(s):  
Cell Fusion ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Biological Properties ◽  
The Other ◽  
Wild Type ◽  
Free Virus ◽  
Other Hand ◽  
The Brain ◽  
Virus Strains

The neurovirulence of two wild type (wt) and seven Subacute Sclerosing Panencephalitis (SSPE) measles virus strains was tested in young adult ferrets by intracerebral (IC) inoculation of infected Vero cell suspensions. Wt strains Edmonston and Woodfolk and SSPE strains Mantooth, Halle, and LEC-S did not produce a detectable encephalitis in the ferrets, but caused a significant formation of serum antibodies against measles virus. SSPE strains LEC, IP-3, Biken, and D.R., on the other hand, were all neurovirulent in ferrets, particularly strain D.R. which caused an acute encephalitis in all inoculated animals. Strain Biken was of particular interest since it caused a subacute encephalitis in four of seven ferrets. The subacute encephalitis was characterized by a long incubation time, persistence of virus in the brain for at least 8 mo, widespread inflammatory lesions, and production of measles virus specific IgG in the brain. A study of the biological properties of the various measles virus strains showed that wt strains Edmonston and Woodfolk and SSPE strains Mantooth, Halle, and LEC-S produced free virus particles in significant titers both in Vero and ferret brain (FB) cultures. Cytopathic effect (CPE) with cell-fusion was marked in Vero cultures, whereas only minimal CPE and no cell-fusion were observed in the FB cultures. SSPE strains LEC, IP-3, Biken, and D.R., on the other hand, were mostly cell-associated in Vero and FB cultures, although atypical cell-free particles were produced by strains Biken and IP-3. All four strains showed cell-fusing activity in FB cultures, particularly strain D.R., which was the only strain that spread more actively by fusion in FB than in Vero cultures. The results are discussed in relation to the neurovirulence of the various measles virus strains in adult ferrets. Pronounced cell-fusing activity in FB cells and cell-association with minimal or no production of cell-free virus seem to be essential to establish a brain infection in the animals.

scholarly journals Weak cis and trans Interactions of the Hemagglutinin with Receptors Trigger Fusion Proteins of Neuropathogenic Measles Virus Isolates

2019 ◽  
Vol 94 (2) ◽  
Author(s):  
Yuta Shirogane ◽  
Takao Hashiguchi ◽  
Yusuke Yanagi
Keyword(s):  
Membrane Fusion ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Target Cells ◽  
Wild Type ◽  
F Protein ◽  
The Brain ◽  
H Protein ◽  
In Cells ◽  
Cell Cell

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.

scholarly journals Measles Virus: Identification in the M Protein Primary Sequence of a Potential Molecular Marker for Subacute Sclerosing Panencephalitis

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Hasan Kweder ◽  
Michelle Ainouze ◽  
Joanna Brunel ◽  
Denis Gerlier ◽  
Evelyne Manet ◽  
...  
Keyword(s):  
Molecular Marker ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
M Protein ◽  
Wild Type ◽  
Virus Identification ◽  
Viral Spread ◽  
M Proteins ◽  
Children And Young Adults ◽  
The Brain

Subacute Sclerosing Panencephalitis (SSPE), a rare lethal disease of children and young adults due to persistence of measles virus (MeV) in the brain, is caused by wild type (wt) MeV. Why MeV vaccine strains never cause SSPE is completely unknown. Hypothesizing that this phenotypic difference could potentially be represented by a molecular marker, we compared glycoprotein and matrix (M) genes from SSPE cases with those from the Moraten vaccine strain, searching for differential structural motifs. We observed that all known SSPE viruses have residues P64, E89, and A209 (PEA) in their M proteins whereas the equivalent residues for vaccine strains are either S64, K89, and T209 (SKT) as in Moraten or PKT. Through the construction of MeV recombinants, we have obtained evidence that the wt MeV-M protein PEA motif, in particular A209, is linked to increased viral spread. Importantly, for the 10 wt genotypes (of 23) that have had their M proteins sequenced, 9 have the PEA motif, the exception being B3, which has PET. Interestingly, cases of SSPE caused by genotype B3 have yet to be reported. In conclusion, our results strongly suggest that the PEA motif is a molecular marker for wt MeV at risk to cause SSPE.

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

1982 ◽  
Vol 40 ◽  
pp. 350-351
Author(s):  
Hannah R. Brown ◽  
Anthony F. Nostro ◽  
Halldor Thormar
Keyword(s):  
Immunoglobulin G ◽  
Human Disease ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Inflammatory Lesions ◽  
Sspe Virus ◽  
Specific Immunoglobulin ◽  
Antibody Titers ◽  
The Brain

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.

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 Complete Genome Sequences of Six Measles Virus Strains

2018 ◽  
Vol 6 (13) ◽  
Author(s):  
My V. T. Phan ◽  
Claudia M. E. Schapendonk ◽  
Bas B. Oude Munnink ◽  
Marion P. G. Koopmans ◽  
Rik L. de Swart ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Complete Genome ◽  
Measles Virus ◽  
Genetic Characterization ◽  
Critical Component ◽  
Wild Type ◽  
Genome Sequences ◽  
Virus Strains ◽  
Generation Sequencing

ABSTRACT Genetic characterization of wild-type measles virus (MV) strains is a critical component of measles surveillance and molecular epidemiology. We have obtained complete genome sequences of six MV strains belonging to different genotypes, using random-primed next generation sequencing.

scholarly journals THE PATHOLOGIC EFFECTS OF STREPTOCOCCI FROM CASES OF POLIOMYELITIS AND OTHER SOURCES

1917 ◽  
Vol 25 (4) ◽  
pp. 557-580 ◽  
Author(s):  
Carroll G. Bull
Keyword(s):  
Spinal Cord ◽  
Guinea Pigs ◽  
The Other ◽  
Laboratory Animals ◽  
Histological Changes ◽  
Other Hand ◽  
Brain And Spinal Cord ◽  
The Brain

Streptococci cultivated from the tonsils of thirty-two cases of poliomyelitis were used to inoculate various laboratory animals. In no case was a condition induced resembling poliomyelitis clinically or pathologically in guinea pigs, dogs, cats, rabbits, or monkeys. On the other hand, a considerable percentage of the rabbits and a smaller percentage of some of the other animals developed lesions due to streptococci. These lesions consisted of meningitis, meningo-encephalitis, abscess of the brain, arthritis, tenosynovitis, myositis, abscess of the kidney, endocarditis, pericarditis, and neuritis. No distinction in the character or frequency of the lesions could be determined between the streptococci derived from poliomyelitic patients and from other sources. Streptococci isolated from the poliomyelitic brain and spinal cord of monkeys which succumbed to inoculation with the filtered virus failed to induce in monkeys any paralysis or the characteristic histological changes of poliomyelitis. These streptococci are regarded as secondary bacterial invaders of the nervous organs. Monkeys which have recovered from infection with streptococci derived from cases of poliomyelitis are not protected from infection with the filtered virus, and their blood does not neutralize the filtered virus in vitro. We have failed to detect any etiologic or pathologic relationship between streptococci and epidemic poliomyelitis in man or true experimental poliomyelitis in the monkey.

Modeling a Particular Decision Process by Using a Modulatory Activation Function

2003 ◽  
Vol 13 (02) ◽  
pp. 111-118
Author(s):  
Jairo Diniz Filho ◽  
Teresa B. Ludermir
Keyword(s):  
Decision Process ◽  
Activation Function ◽  
The Other ◽  
Modular Systems ◽  
Brain Functions ◽  
Mood Changes ◽  
Other Hand ◽  
Neuronal Groups ◽  
The Brain ◽  
Modular Nature

Neuronal groups projecting widely in the brain are being experimentally associated to attention and mood changes. Those groups are known to exert a modulatory effect over other larger groups. On the other hand, some people think of the brain functions as being performed by specialized modular systems. In this work, we propose an architecture of modular nature to explore a particular decision process. We show the importance of the modulatory effect of a special evaluation segment in that process.

scholarly journals 2. Note on the Perception of Musical Sounds

1875 ◽  
Vol 8 ◽  
pp. 342-347
Author(s):  
John G. M'Kendrick
Keyword(s):  
The Other ◽  
Other Hand ◽  
Musical Sounds ◽  
The Brain

Certain individuals appear to be incapable of appreciating musical sounds. They cannot distinguish one melody from another; and if by many repetitions of the melody in their hearing, they at last appear to know it, the addition of one or more of the parts of the harmony again renders the music unrecognisable to them. The question naturally arises, Is this defect owing to any peculiarity in the structure of the internal ear of persons so constituted which prevents them hearing certain sounds, or is it to be referred to the condition of the brain? On the other hand, many have what is termed a “fine ear,” by which we understand the faculty of appreciating, remembering, and, in some cases, of successfully imitating musical sounds. Have those individuals the organ of hearing more delicately developed?

scholarly journals Cell-to-Cell Measles Virus Spread between Human Neurons Is Dependent on Hemagglutinin and Hyperfusogenic Fusion Protein

2018 ◽  
Vol 92 (6) ◽  
Author(s):  
Yuma Sato ◽  
Shumpei Watanabe ◽  
Yoshinari Fukuda ◽  
Takao Hashiguchi ◽  
Yusuke Yanagi ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Acute Infection ◽  
Syncytium Formation ◽  
Wild Type ◽  
F Protein ◽  
Human Neurons ◽  
A Cell ◽  
Nt2 Neurons

ABSTRACTMeasles virus (MV) usually causes acute infection but in rare cases persists in the brain, resulting in subacute sclerosing panencephalitis (SSPE). Since human neurons, an important target affected in the disease, do not express the known MV receptors (signaling lymphocyte activation molecule [SLAM] and nectin 4), how MV infects neurons and spreads between them is unknown. Recent studies have shown that many virus strains isolated from SSPE patients possess substitutions in the extracellular domain of the fusion (F) protein which confer enhanced fusion activity. Hyperfusogenic viruses with such mutations, unlike the wild-type MV, can induce cell-cell fusion even in SLAM- and nectin 4-negative cells and spread efficiently in human primary neurons and the brains of animal models. We show here that a hyperfusogenic mutant MV, IC323-F(T461I)-EGFP (IC323 with a fusion-enhancing T461I substitution in the F protein and expressing enhanced green fluorescent protein), but not the wild-type MV, spreads in differentiated NT2 cells, a widely used human neuron model. Confocal time-lapse imaging revealed the cell-to-cell spread of IC323-F(T461I)-EGFP between NT2 neurons without syncytium formation. The production of virus particles was strongly suppressed in NT2 neurons, also supporting cell-to-cell viral transmission. The spread of IC323-F(T461I)-EGFP was inhibited by a fusion inhibitor peptide as well as by some but not all of the anti-hemagglutinin antibodies which neutralize SLAM- or nectin-4-dependent MV infection, suggesting the presence of a distinct neuronal receptor. Our results indicate that MV spreads in a cell-to-cell manner between human neurons without causing syncytium formation and that the spread is dependent on the hyperfusogenic F protein, the hemagglutinin, and the putative neuronal receptor for MV.IMPORTANCEMeasles virus (MV), in rare cases, persists in the human central nervous system (CNS) and causes subacute sclerosing panencephalitis (SSPE) several years after acute infection. This neurological complication is almost always fatal, and there is currently no effective treatment for it. Mechanisms by which MV invades the CNS and causes the disease remain to be elucidated. We have previously shown that fusion-enhancing substitutions in the fusion protein of MVs isolated from SSPE patients contribute to MV spread in neurons. In this study, we demonstrate that MV bearing the hyperfusogenic mutant fusion protein spreads between human neurons in a cell-to-cell manner. Spread of the virus was inhibited by a fusion inhibitor peptide and antibodies against the MV hemagglutinin, indicating that both the hemagglutinin and hyperfusogenic fusion protein play important roles in MV spread between human neurons. The findings help us better understand the disease process of SSPE.

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