Infection of canine mononuclear leucocytes by measles virus: possible mechanism of protection from canine distemper

1981 ◽  
Vol 27 (10) ◽  
pp. 1128-1131 ◽  
Author(s):  
C. K. Ho ◽  
L. A. Babiuk
Keyword(s):  
Peripheral Blood ◽  
Measles Virus ◽  
Canine Distemper Virus ◽  
Lymphoid Tissues ◽  
Canine Distemper ◽  
Mononuclear Leucocytes

Measles virus was shown to be infectious to canine lymphocytes from peripheral blood as well as from different lymphoid tissues, and the same held true for canine macrophage cultures prepared from peripheral blood. The susceptibility of these leucocytes to measles virus was comparable with that of canine distemper virus. These observations supported the suggestion that interference with canine distemper virus by measles virus could be a possible mechanism of the heterotypic immunity observed in dogs.

scholarly journals Nearby Clusters of Hemagglutinin Residues Sustain SLAM-Dependent Canine Distemper Virus Entry in Peripheral Blood Mononuclear Cells

2005 ◽  
Vol 79 (9) ◽  
pp. 5857-5862 ◽  
Author(s):  
Veronika von Messling ◽  
Numan Oezguen ◽  
Qi Zheng ◽  
Sompong Vongpunsawad ◽  
Werner Braun ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Measles Virus ◽  
Canine Distemper Virus ◽  
Structural Model ◽  
Mononuclear Cells ◽  
Canine Distemper ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Signaling Lymphocytic Activation Molecule

ABSTRACT Signaling lymphocytic activation molecule (SLAM, CD150) is the universal morbillivirus receptor. Based on the identification of measles virus (MV) hemagglutinin (H) amino acids supporting human SLAM-dependent cell entry, we mutated canine distemper virus (CDV) H and identified residues necessary for efficient canine SLAM-dependent membrane fusion. These residues are located in two nearby clusters in a new CDV H structural model. To completely abolish SLAM-dependent fusion, combinations of mutations were necessary. We rescued a SLAM-blind recombinant CDV with six mutations that did not infect ferret peripheral blood mononuclear cells while retaining full infectivity in epithelial cells.

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 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 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.

scholarly journals Canine Distemper Virus Fusion Activation: Critical Role of Residue E123 of CD150/SLAM

2015 ◽  
Vol 90 (3) ◽  
pp. 1622-1637 ◽  
Author(s):  
Mojtaba Khosravi ◽  
Fanny Bringolf ◽  
Silvan Röthlisberger ◽  
Maria Bieringer ◽  
Jürgen Schneider-Schaulies ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Binding Site ◽  
Measles Virus ◽  
Canine Distemper Virus ◽  
Cell Entry ◽  
Physical Interaction ◽  
Canine Distemper ◽  
Attachment Protein ◽  
Binding Interfaces

ABSTRACTMeasles virus (MeV) and canine distemper virus (CDV) possess tetrameric attachment proteins (H) and trimeric fusion proteins, which cooperate with either SLAM or nectin 4 receptors to trigger membrane fusion for cell entry. While the MeV H-SLAM cocrystal structure revealed the binding interface, two distinct oligomeric H assemblies were also determined. In one of the conformations, two SLAM units were sandwiched between two discrete H head domains, thus spotlighting two binding interfaces (“front” and “back”). Here, we investigated the functional relevance of both interfaces in activating the CDV membrane fusion machinery. While alanine-scanning mutagenesis identified five critical regulatory residues in the front H-binding site of SLAM, the replacement of a conserved glutamate residue (E at position 123, replaced with A [E123A]) led to the most pronounced impact on fusion promotion. Intriguingly, while determination of the interaction of H with the receptor using soluble constructs revealed reduced binding for the identified SLAM mutants, no effect was recorded when physical interaction was investigated with the full-length counterparts of both molecules. Conversely, although mutagenesis of three strategically selected residues within the back H-binding site of SLAM did not substantially affect fusion triggering, nevertheless, the mutants weakened the H-SLAM interaction recorded with the membrane-anchored protein constructs. Collectively, our findings support a mode of binding between the attachment protein and the V domain of SLAM that is common to all morbilliviruses and suggest a major role of the SLAM residue E123, located at the front H-binding site, in triggering the fusion machinery. However, our data additionally support the hypothesis that other microdomain(s) of both glycoproteins (including the back H-binding site) might be required to achieve fully productive H-SLAM interactions.IMPORTANCEA complete understanding of the measles virus and canine distemper virus (CDV) cell entry molecular framework is still lacking, thus impeding the rational design of antivirals. Both viruses share many biological features that partially rely on the use of analogous Ig-like host cell receptors, namely, SLAM and nectin 4, for entering immune and epithelial cells, respectively. Here, we provide evidence that the mode of binding between the membrane-distal V domain of SLAM and the attachment protein (H) of morbilliviruses is very likely conserved. Moreover, although structural information revealed two discrete conformational states of H, one of the structures displayed two H-SLAM binding interfaces (“front” and “back”). Our data not only spotlight the front H-binding site of SLAM as the main determinant of membrane fusion promotion but suggest that the triggering efficiency of the viral entry machinery may rely on a local conformational change within the front H-SLAM interactive site rather than the binding affinity.

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