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Special Issue "Morbilliviruses"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 July 2019).

Special Issue Editor

Guest Editor
Dr. Dalan Bailey

The Pirbright Institute, Surrey, United Kingdom
Website | E-Mail
Interests: virus-host interactions; virus receptors; zoonosis; host-range; measles; morbilliviruses; peste des petits ruminants virus; proteomics; viral glycoproteins

Special Issue Information

Dear Colleagues,

Morbilliviruses, especially measles and rinderpest, are significant pathogens that have shaped human and animal health over the centuries. Despite the availability of live attenuated vaccines, they still pose a great risk to human and animal populations, typified by the recent emergence of the small ruminant morbillivirus (peste des petits ruminants virus (PPRV)) in China, North Africa, and Europe, as well as the re-emergence of measles in many developed countries.

Whilst the last 20 years have seen great developments in our understanding of these viruses, in particular the identification of their cellular receptors, there are still many avenues for continued research, for example, the use of measles virus as a potential and effective oncolytic, improved understanding of the genetic determinants of host-range, the impact of eradication on viral ecology, and the structure and function of the viral polymerase... to name just a few!

In this Special Issue, we welcome the morbillivirus research community to submit research papers or review articles related to all aspects of morbillivirus research, which will help to provide a comprehensive overview of this exciting and ever-changing field. Topics of interest include (but are not limited to) molecular biology, epidemiology and ecology, virus-host range and emerging morbilliviruses, pathogenesis and virus-host interactions, and vaccine development and diagnostics.

Dr. Dalan Bailey
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • morbilliviruses 
  • measles virus
  • canine distemper virus 
  • peste des petits ruminants virus 
  • rinderpest virus
  • aquatic mammal morbilliviruses 
  • feline morbillivirus
  • emerging morbilliviruses

Published Papers (9 papers)

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Research

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Open AccessCommunication
Measles Elimination: Identifying Susceptible Sub-Populations to Tailor Immunization Strategies
Viruses 2019, 11(8), 765; https://doi.org/10.3390/v11080765
Received: 31 July 2019 / Revised: 14 August 2019 / Accepted: 16 August 2019 / Published: 20 August 2019
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Abstract
Measles elimination has been identified as a public health priority in Europe for a long time but has not yet been achieved. The World Health Organization (WHO) recommends identification of susceptible sub-populations to target supplementary immunization activities. We used three different sources of [...] Read more.
Measles elimination has been identified as a public health priority in Europe for a long time but has not yet been achieved. The World Health Organization (WHO) recommends identification of susceptible sub-populations to target supplementary immunization activities. We used three different sources of information: retrospective samples investigated for measles IgG between 1997 and 2016, vaccine coverage data from the existing electronic registry for birth cohorts 2015 to 1999, and surveillance data from 2009 until 20 July 2019. We calculated susceptibility by birth cohort using seroprevalence data, adjusting vaccine coverage data with reported effectiveness (93% for the first and 97% for the second dose, respectively), and compared it with measles incidence data, aggregated by birth cohorts and districts. Susceptibility levels for persons 10–41 years (birth cohorts 2007–1976) were 10.4% and thus far above the recommended values of WHO (5%). Older birth cohorts were sufficiently protected. Districts with the highest susceptibility estimates corresponded with districts with the highest incidence rates. Birth cohorts with susceptibility levels > 10% showed a 4.7 increased relative risk of having had more than one measles case. We conclude that retrospective serosurveys are a cheap and useful approach in identifying susceptible sub-populations, especially for older birth cohorts whose coverage data remain scarce. Full article
(This article belongs to the Special Issue Morbilliviruses)
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Open AccessArticle
Specificity of Morbillivirus Hemagglutinins to Recognize SLAM of Different Species
Viruses 2019, 11(8), 761; https://doi.org/10.3390/v11080761
Received: 31 May 2019 / Revised: 15 August 2019 / Accepted: 16 August 2019 / Published: 19 August 2019
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Abstract
Measles virus (MV) and canine distemper virus (CDV) are highly contagious and deadly, forming part of the morbillivirus genus. The receptor recognition by morbillivirus hemagglutinin (H) is important for determining tissue tropism and host range. Recent reports largely urge caution as regards to [...] Read more.
Measles virus (MV) and canine distemper virus (CDV) are highly contagious and deadly, forming part of the morbillivirus genus. The receptor recognition by morbillivirus hemagglutinin (H) is important for determining tissue tropism and host range. Recent reports largely urge caution as regards to the potential expansion of host specificities of morbilliviruses. Nonetheless, the receptor-binding potential in different species of morbillivirus H proteins is largely unknown. Herein, we show that the CDV-H protein binds to the dog signaling lymphocyte activation molecule (SLAM), but not to the human, tamarin, or mouse SLAM. In contrast, MV-H can bind to human, tamarin and dog SLAM, but not to that of mice. Notably, MV binding to dog SLAM showed a lower affinity and faster kinetics than that of human SLAM, and MV exhibits a similar entry activity in dog SLAM- and human SLAM-expressing Vero cells. The mutagenesis study using a fusion assay, based on the MV-H–SLAM complex structure, revealed differences in tolerance for the receptor specificity between MV-H and CDV-H. These results provide insights into H-SLAM specificity related to potential host expansion. Full article
(This article belongs to the Special Issue Morbilliviruses)
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Open AccessArticle
Evolution of Attenuation and Risk of Reversal in Peste des Petits Ruminants Vaccine Strain Nigeria 75/1
Viruses 2019, 11(8), 724; https://doi.org/10.3390/v11080724 (registering DOI)
Received: 20 July 2019 / Revised: 3 August 2019 / Accepted: 5 August 2019 / Published: 7 August 2019
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Abstract
Peste des Petits Ruminants (PPR) is a highly infectious disease caused by a virus of the Morbillivirus genus. The current PPR eradication effort relies mainly on the implementation of massive vaccination campaigns. One of the most widely used PPR vaccines is the Nigeria [...] Read more.
Peste des Petits Ruminants (PPR) is a highly infectious disease caused by a virus of the Morbillivirus genus. The current PPR eradication effort relies mainly on the implementation of massive vaccination campaigns. One of the most widely used PPR vaccines is the Nigeria 75/1 strain obtained after attenuation by 75 serial passages of the wild type isolate in cell cultures. Here we use high throughput deep sequencing of the historical passages that led to the Nigeria 75/1 attenuated strain to understand the evolution of PPRV attenuation and to assess the risk of reversal in different cell types. Comparison of the consensus sequences of the wild type and vaccine strains showed that only 18 fixed mutations separate the two strains. At the earliest attenuation passage at our disposal (passage 47), 12 out of the 18 mutations were already present at a frequency of 100%. Low-frequency variants were identified along the genome in all passages. Sequencing of passages after the vaccine strain showed evidence of genetic drift during cell passages, especially in cells expressing the SLAM receptor targeted by PPRV. However, 15 out of the 18 mutations related to attenuation remained fixed in the population. In vitro experiments suggest that one mutation in the leader region of the PPRV genome affects virus replication. Our results suggest that only a few mutations can have a serious impact on the pathogenicity of PPRV. Risk of reversion to virulence of the attenuated PPRV strain Nigeria 75/1 during serial passages in cell cultures seems low but limiting the number of passages during vaccine production is recommended. Full article
(This article belongs to the Special Issue Morbilliviruses)
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Open AccessArticle
BST2/Tetherin Overexpression Modulates Morbillivirus Glycoprotein Production to Inhibit Cell–Cell Fusion
Viruses 2019, 11(8), 692; https://doi.org/10.3390/v11080692
Received: 13 June 2019 / Revised: 16 July 2019 / Accepted: 20 July 2019 / Published: 30 July 2019
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Abstract
The measles virus (MeV), a member of the genus Morbillivirus, is an established pathogen of humans. A key feature of morbilliviruses is their ability to spread by virus–cell and cell–cell fusion. The latter process, which leads to syncytia formation in vitro and [...] Read more.
The measles virus (MeV), a member of the genus Morbillivirus, is an established pathogen of humans. A key feature of morbilliviruses is their ability to spread by virus–cell and cell–cell fusion. The latter process, which leads to syncytia formation in vitro and in vivo, is driven by the viral fusion (F) and haemagglutinin (H) glycoproteins. In this study, we demonstrate that MeV glycoproteins are sensitive to inhibition by bone marrow stromal antigen 2 (BST2/Tetherin/CD317) proteins. BST2 overexpression causes a large reduction in MeV syncytia expansion. Using quantitative cell–cell fusion assays, immunolabeling, and biochemistry we further demonstrate that ectopically expressed BST2 directly inhibits MeV cell–cell fusion. This restriction is mediated by the targeting of the MeV H glycoprotein, but not other MeV proteins. Using truncation mutants, we further establish that the C-terminal glycosyl-phosphatidylinositol (GPI) anchor of BST2 is required for the restriction of MeV replication in vitro and cell–cell fusion. By extending our study to the ruminant morbillivirus peste des petits ruminants virus (PPRV) and its natural host, sheep, we also confirm this is a broad and cross-species specific phenotype. Full article
(This article belongs to the Special Issue Morbilliviruses)
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Open AccessArticle
Probing Morbillivirus Antisera Neutralization Using Functional Chimerism between Measles Virus and Canine Distemper Virus Envelope Glycoproteins
Viruses 2019, 11(8), 688; https://doi.org/10.3390/v11080688
Received: 29 May 2019 / Revised: 23 July 2019 / Accepted: 25 July 2019 / Published: 27 July 2019
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Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Morbilliviruses)
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Open AccessArticle
A New Genotype of Feline Morbillivirus Infects Primary Cells of the Lung, Kidney, Brain and Peripheral Blood
Viruses 2019, 11(2), 146; https://doi.org/10.3390/v11020146
Received: 7 January 2019 / Revised: 5 February 2019 / Accepted: 7 February 2019 / Published: 9 February 2019
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Abstract
Paramyxoviruses comprise a large number of diverse viruses which in part give rise to severe diseases in affected hosts. A new genotype of feline morbillivirus, tentatively named feline morbillivirus genotype 2 (FeMV-GT2), was isolated from urine of cats with urinary tract diseases. Whole [...] Read more.
Paramyxoviruses comprise a large number of diverse viruses which in part give rise to severe diseases in affected hosts. A new genotype of feline morbillivirus, tentatively named feline morbillivirus genotype 2 (FeMV-GT2), was isolated from urine of cats with urinary tract diseases. Whole genome sequencing showed about 78% nucleotide homology to known feline morbilliviruses. The virus was isolated in permanent cell lines of feline and simian origin. To investigate the cell tropism of FeMV-GT2 feline primary epithelial cells from the kidney, the urinary bladder and the lung, peripheral blood mononuclear cells (PBMC), as well as organotypic brain slice cultures were used for infection experiments. We demonstrate that FeMV-GT2 is able to infect renal and pulmonary epithelial cells, primary cells from the cerebrum and cerebellum, as well as immune cells in the blood, especially CD4+ T cells, CD20+ B cells and monocytes. The cats used for virus isolation shed FeMV-GT2 continuously for several months despite the presence of neutralizing antibodies in the blood. Our results point towards the necessity of increased awareness for this virus when clinical signs of the aforementioned organs are encountered in cats which cannot be explained by other etiologies. Full article
(This article belongs to the Special Issue Morbilliviruses)
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Open AccessArticle
KDELR2 Competes with Measles Virus Envelope Proteins for Cellular Chaperones Reducing Their Chaperone-Mediated Cell Surface Transport
Viruses 2019, 11(1), 27; https://doi.org/10.3390/v11010027
Received: 5 December 2018 / Revised: 21 December 2018 / Accepted: 3 January 2019 / Published: 4 January 2019
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Abstract
Recently, we found that the cytidine deaminase APOBEC3G (A3G) inhibits measles (MV) replication. Using a microarray, we identified differential regulation of several host genes upon ectopic expression of A3G. One of the up-regulated genes, the endoplasmic reticulum (ER) protein retention receptor KDELR2, reduced [...] Read more.
Recently, we found that the cytidine deaminase APOBEC3G (A3G) inhibits measles (MV) replication. Using a microarray, we identified differential regulation of several host genes upon ectopic expression of A3G. One of the up-regulated genes, the endoplasmic reticulum (ER) protein retention receptor KDELR2, reduced MV replication ~5 fold when it was over-expressed individually in Vero and CEM-SS T cells. Silencing of KDELR2 in A3G-expressing Vero cells abrogated the antiviral activity induced by A3G, confirming its role as an A3G-regulated antiviral host factor. Recognition of the KDEL (Lys-Asp-Glu-Leu) motif by KDEL receptors initiates the retrograde transport of soluble proteins that have escaped the ER and play an important role in ER quality control. Although KDELR2 over-expression reduced MV titers in cell cultures, we observed no interaction between KDELR2 and the MV hemagglutinin (H) protein. Instead, KDELR2 retained chaperones in the ER, which are required for the correct folding and transport of the MV envelope glycoproteins H and fusion protein (F) to the cell surface. Our data indicate that KDELR2 competes with MV envelope proteins for binding to calnexin and GRP78/Bip, and that this interaction limits the availability of the chaperones for MV proteins, causing the reduction of virus spread and titers. Full article
(This article belongs to the Special Issue Morbilliviruses)
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Review

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Open AccessReview
Marine Morbilliviruses: Diversity and Interaction with Signaling Lymphocyte Activation Molecules
Viruses 2019, 11(7), 606; https://doi.org/10.3390/v11070606
Received: 23 May 2019 / Revised: 27 June 2019 / Accepted: 29 June 2019 / Published: 3 July 2019
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Abstract
Epidemiological reports of phocine distemper virus (PDV) and cetacean morbillivirus (CeMV) have accumulated since their discovery nearly 30 years ago. In this review, we focus on the interaction between these marine morbilliviruses and their major cellular receptor, the signaling lymphocyte activation molecule (SLAM). [...] Read more.
Epidemiological reports of phocine distemper virus (PDV) and cetacean morbillivirus (CeMV) have accumulated since their discovery nearly 30 years ago. In this review, we focus on the interaction between these marine morbilliviruses and their major cellular receptor, the signaling lymphocyte activation molecule (SLAM). The three-dimensional crystal structure and homology models of SLAMs have demonstrated that 35 residues are important for binding to the morbillivirus hemagglutinin (H) protein and contribute to viral tropism. These 35 residues are essentially conserved among pinnipeds and highly conserved among the Caniformia, suggesting that PDV can infect these animals, but are less conserved among cetaceans. Because CeMV can infect various cetacean species, including toothed and baleen whales, the CeMV-H protein is postulated to have broader specificity to accommodate more divergent SLAM interfaces and may enable the virus to infect seals. In silico analysis of viral H protein and SLAM indicates that each residue of the H protein interacts with multiple residues of SLAM and vice versa. The integration of epidemiological, virological, structural, and computational studies should provide deeper insight into host specificity and switching of marine morbilliviruses. Full article
(This article belongs to the Special Issue Morbilliviruses)
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Open AccessReview
Evolution and Interspecies Transmission of Canine Distemper Virus—An Outlook of the Diverse Evolutionary Landscapes of a Multi-Host Virus
Viruses 2019, 11(7), 582; https://doi.org/10.3390/v11070582
Received: 26 March 2019 / Revised: 13 May 2019 / Accepted: 18 May 2019 / Published: 26 June 2019
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Abstract
Canine distemper virus (CDV) is a worldwide distributed virus which belongs to the genus Morbillivirus within the Paramyxoviridae family. CDV spreads through the lymphatic, epithelial, and nervous systems of domestic dogs and wildlife, in at least six orders and over 20 families of [...] Read more.
Canine distemper virus (CDV) is a worldwide distributed virus which belongs to the genus Morbillivirus within the Paramyxoviridae family. CDV spreads through the lymphatic, epithelial, and nervous systems of domestic dogs and wildlife, in at least six orders and over 20 families of mammals. Due to the high morbidity and mortality rates and broad host range, understanding the epidemiology of CDV is not only important for its control in domestic animals, but also for the development of reliable wildlife conservation strategies. The present review aims to give an outlook of the multiple evolutionary landscapes and factors involved in the transmission of CDV by including epidemiological data from multiple species in urban, wild and peri-urban settings, not only in domestic animal populations but at the wildlife interface. It is clear that different epidemiological scenarios can lead to the presence of CDV in wildlife even in the absence of infection in domestic populations, highlighting the role of CDV in different domestic or wild species without clinical signs of disease mainly acting as reservoirs (peridomestic and mesocarnivores) that are often found in peridomestic habits triggering CDV epidemics. Another scenario is driven by mutations, which generate genetic variation on which random drift and natural selection can act, shaping the genetic structure of CDV populations leading to some fitness compensations between hosts and driving the evolution of specialist and generalist traits in CDV populations. In this scenario, the highly variable protein hemagglutinin (H) determines the cellular and host tropism by binding to signaling lymphocytic activation molecule (SLAM) and nectin-4 receptors of the host; however, the multiple evolutionary events that may have facilitated CDV adaptation to different hosts must be evaluated by complete genome sequencing. This review is focused on the study of CDV interspecies transmission by examining molecular and epidemiological reports based on sequences of the hemagglutinin gene and the growing body of studies of the complete genome; emphasizing the importance of long-term multidisciplinary research that tracks CDV in the presence or absence of clinical signs in wild species, and helping to implement strategies to mitigate the infection. Integrated research incorporating the experience of wildlife managers, behavioral and conservation biologists, veterinarians, virologists, and immunologists (among other scientific areas) and the inclusion of several wild and domestic species is essential for understanding the intricate epidemiological dynamics of CDV in its multiple host infections. Full article
(This article belongs to the Special Issue Morbilliviruses)
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