The In Vivo PDGF Response During Remyelination in Mouse Spinal Cord Following Murine Hepatitis Virus Strain AS9-Induced Transient Demyelination

1998 ◽  
Author(s):  
Jeffrey M. Redwine
Keyword(s):  
Spinal Cord ◽  
Virus Strain ◽  
Hepatitis Virus ◽  
Murine Hepatitis Virus ◽  
Mouse Spinal Cord

scholarly journals In Vivo Two-Photon Imaging of Neurons and Glia in the Mouse Spinal Cord

2012 ◽  
Vol 2012 (12) ◽  
pp. pdb.prot072264-pdb.prot072264 ◽  
Author(s):  
H. Steffens ◽  
F. Nadrigny ◽  
F. Kirchhoff
Keyword(s):  
Spinal Cord ◽  
Mouse Spinal Cord ◽  
Two Photon ◽  
Photon Imaging ◽  
Two Photon Imaging

scholarly journals Variations in Disparate Regions of the Murine Coronavirus Spike Protein Impact the Initiation of Membrane Fusion

2001 ◽  
Vol 75 (6) ◽  
pp. 2792-2802 ◽  
Author(s):  
Dawn K. Krueger ◽  
Sean M. Kelly ◽  
Daniel N. Lewicki ◽  
Rosanna Ruffolo ◽  
Thomas M. Gallagher
Keyword(s):  
Tissue Culture ◽  
Membrane Fusion ◽  
Cultured Cells ◽  
Hepatitis Virus ◽  
Fusion Reaction ◽  
Spike Protein ◽  
Soluble Form ◽  
Fusion Activity ◽  
Murine Hepatitis Virus

ABSTRACT The prototype JHM strain of murine hepatitis virus (MHV) is an enveloped, RNA-containing coronavirus that has been selected in vivo for extreme neurovirulence. This virus encodes spike (S) glycoproteins that are extraordinarily effective mediators of intercellular membrane fusion, unique in their ability to initiate fusion even without prior interaction with the primary MHV receptor, a murine carcinoembryonic antigen-related cell adhesion molecule (CEACAM). In considering the possible role of this hyperactive membrane fusion activity in neurovirulence, we discovered that the growth of JHM in tissue culture selected for variants that had lost murine CEACAM-independent fusion activity. Among the collection of variants, mutations were identified in regions encoding both the receptor-binding (S1) and fusion-inducing (S2) subunits of the spike protein. Each mutation was separately introduced into cDNA encoding the prototype JHM spike, and the set of cDNAs was expressed using vaccinia virus vectors. The variant spikes were similar to that of JHM in their assembly into oligomers, their proteolysis into S1 and S2 cleavage products, their transport to cell surfaces, and their affinity for a soluble form of murine CEACAM. However, these tissue culture-adapted spikes were significantly stabilized as S1-S2 heteromers, and their entirely CEACAM-dependent fusion activity was delayed or reduced relative to prototype JHM spikes. The mutations that we have identified therefore point to regions of the S protein that specifically regulate the membrane fusion reaction. We suggest that cultured cells, unlike certain in vivo environments, select for S proteins with delayed, CEACAM-dependent fusion activities that may increase the likelihood of virus internalization prior to the irreversible uncoating process.

Effect of eicosanoids on induction of procoagulant activity by murine hepatitis virus strain 3 in vitro

1991 ◽  
Vol 42 (6) ◽  
pp. 501-513 ◽  
Author(s):  
S.W. Chung ◽  
S.B. Sinclair ◽  
L.S. Fung ◽  
E.H. Cole ◽  
G.A. Levy
Keyword(s):  
Virus Strain ◽  
Hepatitis Virus ◽  
Procoagulant Activity ◽  
Murine Hepatitis Virus

scholarly journals Chronic in vivo imaging in the mouse spinal cord using an implanted chamber

2012 ◽  
Vol 9 (3) ◽  
pp. 297-302 ◽  
Author(s):  
Matthew J Farrar ◽  
Ida M Bernstein ◽  
Donald H Schlafer ◽  
Thomas A Cleland ◽  
Joseph R Fetcho ◽  
...  
Keyword(s):  
Spinal Cord ◽  
In Vivo Imaging ◽  
Mouse Spinal Cord

scholarly journals Antiviral Effects of Antisense Morpholino Oligomers in Murine Coronavirus Infection Models

2007 ◽  
Vol 81 (11) ◽  
pp. 5637-5648 ◽  
Author(s):  
Renaud Burrer ◽  
Benjamin W. Neuman ◽  
Joey P. C. Ting ◽  
David A. Stein ◽  
Hong M. Moulton ◽  
...  
Keyword(s):  
Cell Culture ◽  
Weight Loss ◽  
Hepatitis Virus ◽  
Antiviral Effect ◽  
High Dose ◽  
Murine Hepatitis Virus ◽  
Experimental Conditions ◽  
Lethal Challenge ◽  
Recent Emergence

ABSTRACT The recent emergence of novel pathogenic human and animal coronaviruses has highlighted the need for antiviral therapies that are effective against a spectrum of these viruses. We have used several strains of murine hepatitis virus (MHV) in cell culture and in vivo in mouse models to investigate the antiviral characteristics of peptide-conjugated antisense phosphorodiamidate morpholino oligomers (P-PMOs). Ten P-PMOs directed against various target sites in the viral genome were tested in cell culture, and one of these (5TERM), which was complementary to the 5′ terminus of the genomic RNA, was effective against six strains of MHV. Further studies were carried out with various arginine-rich peptides conjugated to the 5TERM PMO sequence in order to evaluate efficacy and toxicity and thereby select candidates for in vivo testing. In uninfected mice, prolonged P-PMO treatment did not result in weight loss or detectable histopathologic changes. 5TERM P-PMO treatment reduced viral titers in target organs and protected mice against virus-induced tissue damage. Prophylactic 5TERM P-PMO treatment decreased the amount of weight loss associated with infection under most experimental conditions. Treatment also prolonged survival in two lethal challenge models. In some cases of high-dose viral inoculation followed by delayed treatment, 5TERM P-PMO treatment was not protective and increased morbidity in the treated group, suggesting that P-PMO may cause toxic effects in diseased mice that were not apparent in the uninfected animals. However, the strong antiviral effect observed suggests that with further development, P-PMO may provide an effective therapeutic approach against a broad range of coronavirus infections.

scholarly journals Vulnerability of rat and mouse brain cells to murine hepatitis virus (JHM-strain): Studies in vivo and in vitro

Glia ◽  
1989 ◽  
Vol 2 (2) ◽  
pp. 85-93 ◽  
Author(s):  
M.F. van Berlo ◽  
R. Warringa ◽  
G. Wolswijk ◽  
M. Lopes-Cardozo
Keyword(s):  
Mouse Brain ◽  
Hepatitis Virus ◽  
Brain Cells ◽  
Murine Hepatitis Virus

scholarly journals Role of Endocytosis and Low pH in Murine Hepatitis Virus Strain A59 Cell Entry

2007 ◽  
Vol 81 (19) ◽  
pp. 10758-10768 ◽  
Author(s):  
Patricia Eifart ◽  
Kai Ludwig ◽  
Christoph Böttcher ◽  
Cornelis A. M. de Haan ◽  
Peter J. M. Rottier ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Virus Strain ◽  
Hepatitis Virus ◽  
Low Ph ◽  
Viral Envelope ◽  
Murine Hepatitis Virus ◽  
S Protein ◽  
Fluorescence Confocal Microscopy ◽  
Murine Fibroblast ◽  
Intracellular Compartments

ABSTRACT Infection by the coronavirus mouse hepatitis virus strain A59 (MHV-A59) requires the release of the viral genome by fusion with the respective target membrane of the host cell. Fusion is mediated by the viral S protein. Here, the entry pathway of MHV-A59 into murine fibroblast cells was studied by independent approaches. Infection of cells assessed by plaque reduction assay was strongly inhibited by lysosomotropic compounds and substances that interfere with clathrin-dependent endocytosis, suggesting that MHV-A59 is taken up via endocytosis and delivered to acidic endosomal compartments. Infection was only slightly reduced in the presence of substances inhibiting proteases of endosomal compartments, precluding that the endocytic uptake is required to activate the fusion potential of the S protein by its cleavage. Fluorescence confocal microscopy of labeled MHV-A59 confirmed that virus is taken up via endocytosis. Bright labeling of intracellular compartments suggests their fusion with the viral envelope. No fusion with the plasma membrane was observed at neutral pH conditions. However, when virus was bound to cells and the pH was lowered to 5.0, we observed a strong labeling of the plasma membrane. Electron microscopy revealed low pH triggered conformational alterations of the S ectodomain. Very likely, these alterations are irreversible because low-pH treatment of viruses in the absence of target membranes caused an irreversible loss of the fusion activity. The results imply that endocytosis plays a major role in MHV-A59 infection and the acidic pH of the endosomal compartment triggers a conformational change of the S protein mediating fusion.

scholarly journals Expression of Hemagglutinin Esterase Protein from Recombinant Mouse Hepatitis Virus Enhances Neurovirulence

2005 ◽  
Vol 79 (24) ◽  
pp. 15064-15073 ◽  
Author(s):  
Lubna Kazi ◽  
Arjen Lissenberg ◽  
Richard Watson ◽  
Raoul J. de Groot ◽  
Susan R. Weiss
Keyword(s):  
Receptor Binding ◽  
Demyelinating Disease ◽  
Hepatitis Virus ◽  
Critical Role ◽  
Spike Glycoprotein ◽  
Murine Hepatitis Virus ◽  
Recombinant Viruses ◽  
Viral Spread ◽  
The Central Nervous System

ABSTRACT Murine hepatitis virus (MHV) infection provides a model system for the study of hepatitis, acute encephalitis, and chronic demyelinating disease. The spike glycoprotein, S, which mediates receptor binding and membrane fusion, plays a critical role in MHV pathogenesis. However, viral proteins other than S also contribute to pathogenicity. The JHM strain of MHV is highly neurovirulent and expresses a second spike glycoprotein, the hemagglutinin esterase (HE), which is not produced by MHV-A59, a hepatotropic but only mildly neurovirulent strain. To investigate a possible role for HE in MHV-induced neurovirulence, isogenic recombinant MHV-A59 viruses were generated that produced either (i) the wild-type protein, (ii) an enzymatically inactive HE protein, or (iii) no HE at all (A. Lissenberg, M. M. Vrolijk, A. L. W. van Vliet, M. A. Langereis, J. D. F. de Groot-Mijnes, P. J. M. Rottier, and R. J. de Groot, J. Virol. 79:15054-15063, 2005 [accompanying paper]). A second, mirror set of recombinant viruses was constructed in which, in addition, the MHV-A59 S gene had been replaced with that from MHV-JHM. The expression of HE in combination with A59 S did not affect the tropism, pathogenicity, or spread of the virus in vivo. However, in combination with JHM S, the expression of HE, regardless of whether it retained esterase activity or not, resulted in increased viral spread within the central nervous system and in increased neurovirulence. Our findings suggest that the properties of S receptor utilization and/or fusogenicity mainly determine organ and host cell tropism but that HE enhances the efficiency of infection and promotes viral dissemination, at least in some tissues, presumably by serving as a second receptor-binding protein.

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