scholarly journals Probing Morbillivirus Antisera Neutralization Using Functional Chimerism between Measles Virus and Canine Distemper Virus Envelope Glycoproteins

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 688 ◽  
Author(s):  
Miguel Angel Muñoz-Alía ◽  
Stephen J. Russell
Keyword(s):  
Neutralizing Antibodies ◽  
Measles Virus ◽  
Canine Distemper Virus ◽  
Reverse Genetics ◽  
Canine Distemper ◽  
Virus Envelope ◽  
Live Virus ◽  
Virus Challenge ◽  
Virus Attachment ◽  
Globular Head

Measles virus (MeV) is monotypic. Live virus challenge provokes a broadly protective humoral immune response that neutralizes all known measles genotypes. The two surface glycoproteins, H and F, mediate virus attachment and entry, respectively, and neutralizing antibodies to H are considered the main correlate of protection. Herein, we made improvements to the MeV reverse genetics system and generated a panel of recombinant MeVs in which the globular head domain or stalk region of the H glycoprotein or the entire F protein, or both, were substituted with the corresponding protein domains from canine distemper virus (CDV), a closely related morbillivirus that resists neutralization by measles-immune sera. The viruses were tested for sensitivity to human or guinea pig neutralizing anti-MeV antisera and to ferret anti-CDV antisera. Virus neutralization was mediated by antibodies to both H and F proteins, with H being immunodominant in the case of MeV and F being so in the case of CDV. Additionally, the globular head domains of both MeV and CDV H proteins were immunodominant over their stalk regions. These data shed further light on the factors constraining the evolution of new morbillivirus serotypes.

scholarly journals Establishment of a Rescue System for Canine Distemper Virus

2000 ◽  
Vol 74 (22) ◽  
pp. 10737-10744 ◽  
Author(s):  
Uta Gassen ◽  
Fergal M. Collins ◽  
W. Paul Duprex ◽  
Bert K. Rima
Keyword(s):  
Rna Polymerase ◽  
Measles Virus ◽  
Canine Distemper Virus ◽  
Reverse Genetics ◽  
Syncytium Formation ◽  
Full Length ◽  
Canine Distemper ◽  
Coding Region ◽  
T7 Promoter ◽  
Large Plaque

ABSTRACT Canine distemper virus (CDV) has been rescued from a full-length cDNA clone. Besides Measles virus (MV) andRinderpest virus, a third morbillivirus is now available for genetic analysis using reverse genetics. A plasmid p(+)CDV was constructed by sequential cloning using the Onderstepoort vaccine strain large-plaque-forming variant. The presence of a T7 promoter allowed transcription of full-length antigenomic RNA by a T7 RNA polymerase, which was provided by a host range mutant of vaccinia virus (MVA-T7). Plasmids expressing the nucleocapsid protein, the phosphoprotein, and the viral RNA-dependent RNA polymerase, also under control of a T7 promoter, have been generated. Infection of HeLa cells with MVA-T7 and subsequent transfection of p(+)CDV plus the helper plasmids led to syncytium formation and release of infectious recombinant (r) CDV. Comparison of the rescued virus with the parental virus revealed no major differences in the progression of infection or in the shape and size of syncytia. A genetic tag, consisting of two nucleotide changes within the coding region of the L protein, has been identified in the rCDV genome. Expression by rCDV of all the major viral structural proteins has been demonstrated by immunofluorescence.

scholarly journals Antiviral Screen against Canine Distemper Virus-Induced Membrane Fusion Activity

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 128
Author(s):  
Neeta Shrestha ◽  
Flavio M. Gall ◽  
Jonathan Vesin ◽  
Marc Chambon ◽  
Gerardo Turcatti ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Small Molecule ◽  
High Throughput Screening ◽  
Measles Virus ◽  
Canine Distemper Virus ◽  
Rna Virus ◽  
Preventive Measure ◽  
Close Relative ◽  
Fusion Activity ◽  
Canine Distemper

Canine distemper virus (CDV), a close relative of the human pathogen measles virus (MeV), is an enveloped, negative sense RNA virus that belongs to the genus Morbillivirus and causes severe diseases in dogs and other carnivores. Although the vaccination is available as a preventive measure against the disease, the occasional vaccination failure highlights the importance of therapeutic alternatives such as antivirals against CDV. The morbilliviral cell entry system relies on two interacting envelope glycoproteins: the attachment (H) and fusion (F) proteins. Here, to potentially discover novel entry inhibitors targeting CDV H, F and/or the cognate receptor: signaling lymphocyte activation molecule (SLAM) proteins, we designed a quantitative cell-based fusion assay that matched high-throughput screening (HTS) settings. By screening two libraries of small molecule compounds, we successfully identified two membrane fusion inhibitors (F2736-3056 and F2261-0043). Although both inhibitors exhibited similarities in structure and potency with the small molecule compound 3G (an AS-48 class morbilliviral F-protein inhibitor), F2736-3056 displayed improved efficacy in blocking fusion activity when a 3G-escape variant was employed. Altogether, we present a cell-based fusion assay that can be utilized not only to discover antiviral agents against CDV but also to dissect the mechanism of morbilliviral-mediated cell-binding and cell-to-cell fusion activity.

scholarly journals Molecular evidence for vaccine-induced canine distemper virus and canine adenovirus 2 coinfection in a fennec fox

2020 ◽  
Vol 32 (4) ◽  
pp. 598-603
Author(s):  
Kenichi Tamukai ◽  
Shohei Minami ◽  
Rio Kurihara ◽  
Hiroshi Shimoda ◽  
Ikki Mitsui ◽  
...  
Keyword(s):  
Inclusion Bodies ◽  
Canine Distemper Virus ◽  
Neuronal Degeneration ◽  
Molecular Evidence ◽  
Intranuclear Inclusions ◽  
Canine Distemper ◽  
Live Virus ◽  
Bronchial Epithelial ◽  
Eosinophilic Inclusion ◽  
The Brain

A 61-d-old fennec fox ( Vulpes zerda), 11 d after receiving a multivalent, modified-live virus vaccine containing canine distemper virus (CDV), canine adenovirus 2 (CAdV-2), parainfluenza virus, parvovirus, and canine coronavirus, developed oculonasal discharge, and subsequently convulsions, and hemoptysis, and died. Microscopic changes in the cerebrum were evident, including neuronal degeneration and necrosis; intracytoplasmic eosinophilic inclusion bodies were observed in astrocytes. CDV was detected in the brain tissue by immunohistochemistry. Pulmonary lesions of multifocal necrotizing bronchopneumonia had Cowdry type A intranuclear inclusions in the bronchial epithelial cells. Electron microscopy revealed crystalline arrays of adenovirus-like particles within the intranuclear inclusions. Additionally, the hemagglutinin gene of CDV and the CAdV-2 DNA polymerase gene were detected in the fennec fox; sequence analysis showed 100% identity with those of the vaccine strain viruses. To our knowledge, vaccine-induced CDV and CAdV-2 coinfections using molecular analysis have not been reported previously. Therefore, vaccine strains should be considered prior to CDV vaccination in nondomestic carnivores.

scholarly journals Prevalence of canine distemper virus in wild mustelids in the Czech Republic and a case of canine distemper in young stone martens

2008 ◽  
Vol 52 (No. 2) ◽  
pp. 69-73 ◽  
Author(s):  
L. Pavlacik ◽  
V. Celer ◽  
P. Koubek ◽  
I. Literak
Keyword(s):  
Czech Republic ◽  
Neutralizing Antibodies ◽  
Canine Distemper Virus ◽  
Meles Meles ◽  
Acute Stage ◽  
Direct Immunofluorescence ◽  
Canine Distemper ◽  
The Czech Republic ◽  
Mustela Nivalis ◽  
Pine Martens

Between 2001 and 2003, a total of 194 samples of brain tissues of wild mustelids from the Czech Republic were tested for the presence of canine distemper virus (CDV) by direct immunofluorescence examination. Out of 21 animals exhibiting symptoms of the disease or changed behaviour, one mustelid was CDV positive (5% prevalence). In this group, 1 out of 18 stone martens (<i>Martes foina</i>) was CDV positive, while 2 pine martens (<i>Martes martes</i>) and 1 Eurasian badger (<i>Meles meles</i>) were CDV negative. Of 173 animals with unknown case history, 1 sample was positive (0.6% prevalence). In this group of animals, 1 out of 19 Eurasian badgers was positive, and stone martens (<i>n</i> = 96), pine martens (<i>n</i> = 4), polecats (<i>Mustela putorius</i>) ((<i>n</i> = 28), steppe polecats (<i>Mustela eversmani</i>) (<i>n</i> = 4), common weasels (<i>Mustela nivalis</i>) (<i>n</i> = 4), stoats (<i>Mustela erminea</i>) (<i>n</i> = 3) and American minks (<i>Mustela vison</i>) (<i>n</i> = 19) were negative. Clinical distemper was demonstrated in three stone marten pup siblings. In two of the siblings, CDV was demonstrated in footpads. The third of the siblings survived the acute stage of the disease and had virus neutralizing antibodies from the end of the acute stage until 6 months after the end of the acute stage, with a maximum antibody titre of 32. During the acute stage and 7 months after the end of the acute stage, no virus neutralizing antibodies were found.

Vaccination of puppies with a lipid-formulated plasmid vaccine protects against a severe canine distemper virus challenge

Vaccine ◽  
2003 ◽  
Vol 21 (11-12) ◽  
pp. 1099-1102 ◽  
Author(s):  
Laurent Fischer ◽  
Jean Philippe Tronel ◽  
Jules Minke ◽  
Simona Barzu ◽  
Philippe Baudu ◽  
...  
Keyword(s):  
Canine Distemper Virus ◽  
Canine Distemper ◽  
Virus Challenge ◽  
Plasmid Vaccine

scholarly journals Recovery of NanoLuc Luciferase-Tagged Canine Distemper Virus for Facilitating Rapid Screening of Antivirals in vitro

2020 ◽  
Vol 7 ◽  
Author(s):  
Fuxiao Liu ◽  
Qianqian Wang ◽  
Yilan Huang ◽  
Ning Wang ◽  
Youming Zhang ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Canine Distemper Virus ◽  
Reverse Genetics ◽  
Rapid Screening ◽  
Canine Distemper ◽  
Virus Propagation ◽  
The Family ◽  
Conventional Methods

Canine distemper virus (CDV), belonging to the genus Morbillivirus in the family Paramyxoviridae, is a highly contagious pathogen, affecting various domestic, and wild carnivores. Conventional methods are too cumbersome to be used for high-throughput screening of anti-CDV drugs. In this study, a recombinant CDV was rescued using reverse genetics for facilitating screening of anti-CDV drug in vitro. The recombinant CDV could stably express the NanoLuc® luciferase (NLuc), a novel enzyme that was smaller and “brighter” than others. The intensity of NLuc-catalyzed luminescence reaction indirectly reflected the anti-CDV effect of a certain drug, due to a positive correlation between NLuc expression and virus propagation in vitro. Based on such a characteristic feature, the recombinant CDV was used for anti-CDV assays on four drugs (ribavirin, moroxydine hydrochloride, 1-adamantylamine hydrochloride, and tea polyphenol) via analysis of luciferase activity, instead of via conventional methods. The result showed that out of these four drugs, only the ribavirin exhibited a detectable anti-CDV effect. The NLuc-tagged CDV would be a rapid tool for high-throughput screening of anti-CDV drugs.

scholarly journals Canine Distemper Virus Uses both the Anterograde and the Hematogenous Pathway for Neuroinvasion

2006 ◽  
Vol 80 (19) ◽  
pp. 9361-9370 ◽  
Author(s):  
Penny A. Rudd ◽  
Roberto Cattaneo ◽  
Veronika von Messling
Keyword(s):  
Measles Virus ◽  
Canine Distemper Virus ◽  
Fluorescent Protein ◽  
Early Time ◽  
Olfactory Nerve ◽  
The Body ◽  
Target Cells ◽  
Canine Distemper ◽  
Invasion Routes ◽  
Green Fluorescent

ABSTRACT Canine distemper virus (CDV), a member of the Morbillivirus genus that also includes measles virus, frequently causes neurologic complications, but the routes and timing of CDV invasion of the central nervous system (CNS) are poorly understood. To characterize these events, we cloned and sequenced the genome of a neurovirulent CDV (strain A75/17) and produced an infectious cDNA that expresses the green fluorescent protein. This virus fully retained its virulence in ferrets: the course and signs of disease were equivalent to those of the parental isolate. We observed CNS invasion through two distinct pathways: anterogradely via the olfactory nerve and hematogenously through the choroid plexus and cerebral blood vessels. CNS invasion only occurred after massive infection of the lymphatic system and spread to the epithelial cells throughout the body. While at early time points, mostly immune and endothelial cells were infected, the virus later spread to glial cells and neurons. Together, the results suggest similarities in the timing, target cells, and CNS invasion routes of CDV, members of the Morbillivirus genus, and even other neurovirulent paramyxoviruses like Nipah and mumps viruses.

scholarly journals Canine Distemper Virus and Measles Virus Fusion Glycoprotein Trimers: Partial Membrane-Proximal Ectodomain Cleavage Enhances Function

2004 ◽  
Vol 78 (15) ◽  
pp. 7894-7903 ◽  
Author(s):  
Veronika von Messling ◽  
Dragana Milosevic ◽  
Patricia Devaux ◽  
Roberto Cattaneo
Keyword(s):  
Amino Acids ◽  
Protein Function ◽  
Measles Virus ◽  
Canine Distemper Virus ◽  
Transmembrane Domain ◽  
Fusion Pore ◽  
Canine Distemper ◽  
Furin Cleavage ◽  
F Protein ◽  
Membrane Processing

ABSTRACT The trimeric fusion (F) glycoproteins of morbilliviruses are activated by furin cleavage of the precursor F0 into the F1 and F2 subunits. Here we show that an additional membrane-proximal cleavage occurs and modulates F protein function. We initially observed that the ectodomain of approximately one in three measles virus (MV) F proteins is cleaved proximal to the membrane. Processing occurs after cleavage activation of the precursor F0 into the F1 and F2 subunits, producing F1a and F1b fragments that are incorporated in viral particles. We also detected the F1b fragment, including the transmembrane domain and cytoplasmic tail, in cells expressing the canine distemper virus (CDV) or mumps virus F protein. Six membrane-proximal amino acids are necessary for efficient CDV F1a/b cleavage. These six amino acids can be exchanged with the corresponding MV F protein residues of different sequence without compromising function. Thus, structural elements of different sequence are functionally exchangeable. Finally, we showed that the alteration of a block of membrane-proximal amino acids results in diminished fusion activity in the context of a recombinant CDV. We envisage that selective loss of the membrane anchor in the external subunits of circularly arranged F protein trimers may disengage them from pulling the membrane centrifugally, thereby facilitating fusion pore formation.

Sign in / Sign up

Export Citation Format

Share Document