scholarly journals Measles fusion complexes from central nervous system clinical isolates: decreased interaction between hemagglutinin and fusion proteins

2021 ◽  
Author(s):  
Cyrille Mathieu ◽  
Tiago Nascimento Figueira ◽  
Amanda R Decker ◽  
Marion Ferren ◽  
Francesca Tiziana Bovier ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Viral Entry ◽  
Measles Virus ◽  
Single Amino Acid ◽  
Cns Infection ◽  
Wild Type ◽  
Single Amino Acid Change ◽  
The Central Nervous System ◽  
H Protein

Measles virus (MeV) viral entry is mediated by a fusion complex comprised of a receptor-binding protein (hemagglutinin, H) and a fusion protein (F). The wild-type H/F complex requires interaction with specific proteinaceous receptors (CD150/SLAM and nectin-4) in order to be activated. In contrast, the H/F complexes isolated from viruses infecting the central nervous system (CNS) do not require a specific receptor. A single amino acid change in the F protein (L454W) was previously identified in two patients with lethal sequelae of MeV CNS infection, and the F bearing this mutation mediates fusion even without the H protein. We show here that viruses bearing the L454W fusion complex are less efficient than wt virus at targeting receptor-expressing cells and that this defect is associated with a decreased interaction between the H and the F proteins.

scholarly journals Measles Virus Bearing Measles Inclusion Body Encephalitis-Derived Fusion Protein Is Pathogenic after Infection via the Respiratory Route

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Cyrille Mathieu ◽  
Marion Ferren ◽  
Eric Jurgens ◽  
Claire Dumont ◽  
Ksenia Rybkina ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Animal Models ◽  
Fusion Protein ◽  
Inclusion Body ◽  
Measles Virus ◽  
Antiviral Treatment ◽  
Single Amino Acid ◽  
Cns Infection ◽  
Viral Fusion

ABSTRACTA clinical isolate of measles virus (MeV) bearing a single amino acid alteration in the viral fusion protein (F; L454W) was previously identified in two patients with lethal sequelae of MeV central nervous system (CNS) infection. The mutation dysregulated the viral fusion machinery so that the mutated F protein mediated cell fusion in the absence of known MeV cellular receptors. While this virus could feasibly have arisen via intrahost evolution of the wild-type (wt) virus, it was recently shown that the same mutation emerged under the selective pressure of small-molecule antiviral treatment. Under these conditions, a potentially neuropathogenic variant emerged outside the CNS. While CNS adaptation of MeV was thought to generate viruses that are less fit for interhost spread, we show that two animal models can be readily infected with CNS-adapted MeV via the respiratory route. Despite bearing a fusion protein that is less stable at 37°C than the wt MeV F, this virus infects and replicates in cotton rat lung tissue more efficiently than the wt virus and is lethal in a suckling mouse model of MeV encephalitis even with a lower inoculum. Thus, either during lethal MeV CNS infection or during antiviral treatmentin vitro, neuropathogenic MeV can emerge, can infect new hosts via the respiratory route, and is more pathogenic (at least in these animal models) than wt MeV.IMPORTANCEMeasles virus (MeV) infection can be severe in immunocompromised individuals and lead to complications, including measles inclusion body encephalitis (MIBE). In some cases, MeV persistence and subacute sclerosing panencephalitis (SSPE) occur even in the face of an intact immune response. While they are relatively rare complications of MeV infection, MIBE and SSPE are lethal. This work addresses the hypothesis that despite a dysregulated viral fusion complex, central nervous system (CNS)-adapted measles virus can spread outside the CNS within an infected host.

Distribution of measles virus in the central nervous system of HIV-seropositive children

1998 ◽  
Vol 96 (6) ◽  
pp. 637-642 ◽  
Author(s):  
S. McQuaid ◽  
S. L. Cosby ◽  
K. Koffi ◽  
M. Honde ◽  
J. Kirk ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Measles Virus ◽  
The Central Nervous System ◽  
Hiv Seropositive

Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice overexpressing wild-type prion proteins

Cell ◽  
1994 ◽  
Vol 76 (1) ◽  
pp. 117-129 ◽  
Author(s):  
David Westaway ◽  
Stephen J. DeArmond ◽  
Juliana Cayetano-Canlas ◽  
Darlene Groth ◽  
Dallas Foster ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Central Nervous System ◽  
Nervous System ◽  
Transgenic Mice ◽  
Peripheral Nerves ◽  
Prion Proteins ◽  
Wild Type ◽  
The Central Nervous System

Measles Virus Genome in Infections of the Central Nervous System

1981 ◽  
Vol 144 (2) ◽  
pp. 154-160 ◽  
Author(s):  
A. T. Haase ◽  
P. Swoveland ◽  
L. Stowring ◽  
P. Ventura ◽  
K. P. Johnson ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Measles Virus ◽  
Virus Genome ◽  
The Central Nervous System

scholarly journals Delayed development of specific thyroid hormone-regulated events in transthyretin null mice

2013 ◽  
Vol 304 (1) ◽  
pp. E23-E31 ◽  
Author(s):  
Julie A. Monk ◽  
Natalie A. Sims ◽  
Katarzyna M. Dziegielewska ◽  
Roy E. Weiss ◽  
Robert G. Ramsay ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Thyroid Hormone ◽  
Bone Growth ◽  
Circulatory System ◽  
Goblet Cells ◽  
Wild Type ◽  
The Central Nervous System ◽  
Delayed Growth

Thyroid hormones (THs) are vital for normal postnatal development. Extracellular TH distributor proteins create an intravascular reservoir of THs. Transthyretin (TTR) is a TH distributor protein in the circulatory system and is the only TH distributor protein synthesized in the central nervous system. We investigated the phenotype of TTR null mice during development. Total and free 3′,5′,3,5-tetraiodo-l-thyronine (T4) and free 3′,3,5-triiodo-l-thyronine (T3) in plasma were significantly reduced in 14-day-old (P14) TTR null mice. TTR null mice also displayed a delayed suckling-to-weaning transition, decreased muscle mass, delayed growth, and retarded longitudinal bone growth. In addition, ileums from postnatal day 0 (P0) TTR null mice displayed disordered architecture and contained fewer goblet cells than wild type. Protein concentrations in cerebrospinal fluid from P0 and P14 TTR null mice were higher than in age-matched wild-type mice. In contrast to the current literature based on analyses of adult TTR null mice, our results demonstrate that TTR has an important and nonredundant role in influencing the development of several organs.

scholarly journals Borna Disease Virus Accelerates Inflammation and Disease Associated with Transgenic Expression of Interleukin-12 in the Central Nervous System

2002 ◽  
Vol 76 (23) ◽  
pp. 12223-12232 ◽  
Author(s):  
Susanna Freude ◽  
Jürgen Hausmann ◽  
Markus Hofer ◽  
Ngan Pham-Mitchell ◽  
Iain L. Campbell ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transgenic Mice ◽  
Disease Virus ◽  
Biologically Active ◽  
Interleukin 12 ◽  
Wild Type ◽  
Borna Disease Virus ◽  
The Central Nervous System ◽  
Borna Disease

ABSTRACT Targeted expression of biologically active interleukin-12 (IL-12) in astrocytes of the central nervous system (CNS) results in spontaneous neuroimmunological disease of aged mice. Borna disease virus (BDV) can readily multiply in the mouse CNS but does not trigger disease in most strains. Here we show that a large percentage of IL-12 transgenic mice developed severe ataxia within 5 to 10 weeks after infection with BDV. By contrast, no disease developed in mock-infected IL-12 transgenic and wild-type mice until 4 months of age. Neurological symptoms were rare in infected wild-type animals, and if they occurred, these were milder and appeared later. Histological analyses showed that the cerebellum of infected IL-12 transgenic mice, which is the brain region with strongest transgene expression, contained large numbers of CD4+ and CD8+ T cells as well as lower numbers of B cells, whereas other parts of the CNS showed only mild infiltration by lymphocytes. The cerebellum of diseased mice further showed severe astrogliosis, calcifications and signs of neurodegeneration. BDV antigen and nucleic acids were present in lower amounts in the inflamed cerebellum of infected transgenic mice than in the noninflamed cerebellum of infected wild-type littermates, suggesting that IL-12 or IL-12-induced cytokines exhibited antiviral activity. We propose that BDV infection accelerates the frequency by which immune cells such as lymphocytes and NK cells enter the CNS and then respond to IL-12 present in the local milieu causing disease. Our results illustrate that infection of the CNS with a virus that is benign in certain hosts can be harmful in such normally disease-resistant hosts if the tissue is unfavorably preconditioned by proinflammatory cytokines.

scholarly journals Type I Interferon Receptor Signaling Drives Selective Permissiveness of Astrocytes and Microglia to Measles Virus during Brain Infection

2019 ◽  
Vol 93 (13) ◽  
Author(s):  
Jeremy Charles Welsch ◽  
Benjamin Charvet ◽  
Sebastien Dussurgey ◽  
Omran Allatif ◽  
Noemie Aurine ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Measles Virus ◽  
Type I Interferon ◽  
Proteome Analysis ◽  
Secreted Proteins ◽  
Type I ◽  
Brain Infection ◽  
The Central Nervous System

ABSTRACTFatal neurological syndromes can occur after measles virus (MeV) infection of the brain. The mechanisms controlling MeV spread within the central nervous system (CNS) remain poorly understood. We analyzed the role of type I interferon (IFN-I) receptor (IFNAR) signaling in the control of MeV infection in a murine model of brain infection. Using organotypic brain cultures (OBC) from wild-type and IFNAR-knockout (IFNARKO) transgenic mice ubiquitously expressing the human SLAM (CD150) receptor, the heterogeneity of the permissiveness of different CNS cell types to MeV infection was characterized. In the absence of IFNAR signaling, MeV propagated significantly better in explant slices. In OBC from IFNAR-competent mice, while astrocytes and microglia were infected on the day of explant preparation, they became refractory to infection with time, in contrast to neurons and oligodendrocytes, which remained permissive to infection. This selective loss of permissiveness to MeV infection was not observed in IFNARKOmouse OBC. Accordingly, the development of astrogliosis related to the OBC procedure was exacerbated in the presence of IFNAR signaling. In the hippocampus, this astrogliosis was characterized by a change in the astrocyte phenotype and by an increase of IFN-I transcripts. A proteome analysis showed the upregulation of 84 out of 111 secreted proteins. In the absence of IFNAR, only 27 secreted proteins were upregulated, and none of these were associated with antiviral activities. Our results highlight the essential role of the IFN-I response in astrogliosis and in the permissiveness of astrocytes and microglia that could control MeV propagation throughout the CNS.IMPORTANCEMeasles virus (MeV) can infect the central nervous system (CNS), with dramatic consequences. The mechanisms controlling MeV invasion of the CNS remain ill-defined since most previous data were obtained from postmortem analysis. Here, we highlight for the first time the crucial role of the type I interferon (IFN-I) response not only in the control of CNS invasion but also in the early permissiveness of glial cells to measles virus infection.

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