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Viruses Jun 2014Neoplastic diseases represent one of the most common causes of death among humans and animals. Currently available and applied therapeutic options often remain... (Review)
Review
Neoplastic diseases represent one of the most common causes of death among humans and animals. Currently available and applied therapeutic options often remain insufficient and unsatisfactory, therefore new and innovative strategies and approaches are highly needed. Periodically, oncolytic viruses have been in the center of interest since the first anecdotal description of their potential usefulness as an anti-tumor treatment concept. Though first reports referred to an incidental measles virus infection causing tumor regression in a patient suffering from lymphoma several decades ago, no final treatment concept has been developed since then. However, numerous viruses, such as herpes-, adeno- and paramyxoviruses, have been investigated, characterized, and modified with the aim to generate a new anti-cancer treatment option. Among the different viruses, measles virus still represents a highly interesting candidate for such an approach. Numerous different tumors of humans including malignant lymphoma, lung and colorectal adenocarcinoma, mesothelioma, and ovarian cancer, have been studied in vitro and in vivo as potential targets. Moreover, several concepts using different virus preparations are now in clinical trials in humans and may proceed to a new treatment option. Surprisingly, only few studies have investigated viral oncolysis in veterinary medicine. The close relationship between measles virus (MV) and canine distemper virus (CDV), both are morbilliviruses, and the fact that numerous tumors in dogs exhibit similarities to their human counterpart, indicates that both the virus and species dog represent a highly interesting translational model for future research in viral oncolysis. Several recent studies support such an assumption. It is therefore the aim of the present communication to outline the mechanisms of morbillivirus-mediated oncolysis and to stimulate further research in this potentially expanding field of viral oncolysis in a highly suitable translational animal model for the benefit of humans and dogs.
Topics: Animals; Distemper Virus, Canine; Dogs; Humans; Measles virus; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 24921409
DOI: 10.3390/v6062340 -
Journal of Clinical Microbiology Mar 2017During measles outbreaks, it is important to be able to rapidly distinguish between measles cases and vaccine reactions to avoid unnecessary outbreak response measures...
During measles outbreaks, it is important to be able to rapidly distinguish between measles cases and vaccine reactions to avoid unnecessary outbreak response measures such as case isolation and contact investigations. We have developed a real-time reverse transcription-PCR (RT-PCR) method specific for genotype A measles virus (MeV) (MeVA RT-quantitative PCR [RT-qPCR]) that can identify measles vaccine strains rapidly, with high throughput, and without the need for sequencing to determine the genotype. We have evaluated the method independently in three measles reference laboratories using two platforms, the Roche LightCycler 480 system and the Applied Biosystems (ABI) 7500 real-time PCR system. In comparison to the standard real-time RT-PCR method, the MeVA RT-qPCR showed 99.5% specificity for genotype A and 94% sensitivity for both platforms. The new assay was able to detect RNA from five currently used vaccine strains, AIK-C, CAM-70, Edmonston-Zagreb, Moraten, and Shanghai-191. The MeVA RT-qPCR assay has been used successfully for measles surveillance in reference laboratories, and it could be readily deployed to national and subnational laboratories on a wide scale.
Topics: Genotype; Humans; Measles Vaccine; Measles virus; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity
PubMed: 27852670
DOI: 10.1128/JCM.01879-16 -
Virus Research May 2017In accordance with the goal of the World Health Organization Regional Office for Europe, the Italian National Measles and Rubella Elimination Plan aimed to interrupt...
In accordance with the goal of the World Health Organization Regional Office for Europe, the Italian National Measles and Rubella Elimination Plan aimed to interrupt indigenous measles transmission in Italy by the end of 2015. However, from 2013 to 2015, Italy experienced high measles burden with 4902 measles cases (49.3% laboratory-confirmed) reported to the enhanced measles surveillance system (cumulative incidence in the triennium reference period: 2.4/100,000 population). The measles elimination goal was not reached. Laboratory surveillance of measles circulating genotypes is performed by the Measles and Rubella National Reference Laboratory (NRL) at the Italian National Institute of Health (Istituto Superiore di Sanità - ISS), in Rome. Samples received from 1 January 2013-31 December 2015 were analysed. Those positive for measles genome by molecular tests were sequenced and phylogenetically analysed. Phylogenetic analysis performed by NRL identified that genotypes D4 and D8 were endemic and co-circulated in 2011-2013: study results show that genotype D4 disappeared during 2013. Sporadic cases were associated to genotype B3 during 2011-2013, which became endemic in Italy during 2014 and co-circulated with D8 until 2015. Sporadic cases were found belonging to genotypes D9 and H1 all over the period in exam. Similar trend has been observed in European WHO Region.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Disease Outbreaks; Female; Genotype; Humans; Infant; Italy; Male; Measles; Measles virus; Middle Aged; Molecular Epidemiology; Phylogeny; RNA, Viral; Sentinel Surveillance; Young Adult
PubMed: 28522332
DOI: 10.1016/j.virusres.2017.05.009 -
Virology Jun 1995The initial site of virus replication during measles infection is in the epithelial cells of the respiratory tract. We have investigated measles virus infection of two... (Comparative Study)
Comparative Study
The initial site of virus replication during measles infection is in the epithelial cells of the respiratory tract. We have investigated measles virus infection of two types of polarized epithelial cells to determine if entry and/or release of the virus is confined to either the apical or the basolateral plasma membrane. The Caco-2 line of human intestinal epithelial cells and the polarized Vero C1008 monkey kidney cell line were grown on permeable supports and inoculated either through the apical or basolateral surfaces. Cells exposed to virus in the apical medium showed high levels of synthesis of virus-specific proteins, whereas no synthesis of viral proteins was detected in cells inoculated at the basolateral surface. Virus titers derived from apically infected cells were found to be about 1000-fold greater than titers derived from cells infected at the basolateral surface. Indirect immunofluorescence results also demonstrated that expression of measles viral antigens occurs at high levels only when input virions are inoculated at the apical surface. To investigate the localization of CD46 and moesin, which are receptors for measles virus, Caco-2 cells were incubated with monoclonal antibodies against CD46 or moesin followed by 125I-labeled anti-mouse Ig. The results indicate that CD46 is expressed preferentially on the apical membranes while moesin appears to be present at similar levels on both surfaces. Release of the virus was also examined and found to be polarized as well. Virus was released into the apical medium at up to 1000-fold higher titers than virus released into the basolateral medium. These results demonstrate that in two epithelial cell types measles virus preferentially enters and is released from epithelial cells in a polarized fashion through the apical plasma membrane.
Topics: Animals; Antibodies, Viral; Antigens, CD; Cell Line; Cell Membrane; Chlorocebus aethiops; Cricetinae; Epithelium; HeLa Cells; Humans; Kidney; Kinetics; Measles virus; Membrane Cofactor Protein; Membrane Glycoproteins; Microscopy, Electron; Receptors, Virus; Time Factors; Vero Cells; Virus Replication
PubMed: 7793085
DOI: 10.1006/viro.1995.1320 -
Journal of Virology Dec 1975Replication of Edmonston strain measles virus was studied in several human lymphoblast lines, as well as in defined subpopulations of circulating human leukocytes. It...
Replication of Edmonston strain measles virus was studied in several human lymphoblast lines, as well as in defined subpopulations of circulating human leukocytes. It was found that measles virus can productively infect T cells, B cells, and monocytes from human blood. These conclusions were derived from infectious center studies on segregated cell populations, as well as from ultrastructural analyses on cells labeled with specific markers. In contrast, mature polymorphonuclear cells failed to synthesize measles virus nucleocapsids even after infection at a relatively high multiplicity of infection. Measles virus replicated more efficiently in lymphocytes stimulated with mitogens than in unstimulated cells. However, both phytohemagglutinin and pokeweed mitogen had a negligible stimulatory effect on viral synthesis in purified populations of monocytes. In all instances the efficiency of measles virus replication by monocytes was appreciably less than that of mitogenically stimulated lymphocytes or of continuously culture lymphoblasts. Under standard conditions of infection, all of the surveyed lymphoblast lines produced equivalent amounts of measles virus regardless of the major histocompatibility (HL-A) haplotype. Hence, no evidence was found that the HL-A3,7 haplotype conferred either an advantage or disadvantage with respect to measles virus synthesis in an immunologically neutral environment. A persistent infection with measles virus could be established in both T and B lymphoblasts. The release of infectious virus from such persistently infected cells was stable over a period of several weeks and was approximately 100-fold less than peak viral titers obtained in each respective line after acute infection.
Topics: B-Lymphocytes; Cell Line; Cells, Cultured; Humans; Lectins; Leukocytes; Measles virus; Mitogens; Monocytes; T-Lymphocytes; Time Factors; Virus Replication
PubMed: 1081602
DOI: 10.1128/JVI.16.6.1638-1649.1975 -
Microbes and Infection Apr 2009Subacute sclerosing panencephalitis (SSPE) is caused by variants of wild-type measles virus (MV). Such MV variants lack almost completely the ability to produce...
Single-point mutations of the M protein of a measles virus variant obtained from a patient with subacute sclerosing panencephalitis critically affect solubility and subcellular localization of the M protein and cell-free virus production.
Subacute sclerosing panencephalitis (SSPE) is caused by variants of wild-type measles virus (MV). Such MV variants lack almost completely the ability to produce cell-free progeny virus. We recently isolated an MV variant that has only three amino acid mutations (L165P,L250P and Y282H) in the M protein compared with MV field isolates of the same genotype. In the present study, we analyzed the significance of these mutations with regard to the characteristics of the M protein and progeny virus production. We found that each of the three mutations rendered the M protein insoluble in 0.5% Triton X-100 and altered its subcellular localization, either when ectopically expressed alone using a plasmid-based expression system or when expressed in the context of viral replication. Moreover, each of the three mutations markedly, but not completely, impaired the ability of MV to produce cell-free progeny virus, with the degree of impairment being the same as for all three mutations together. These results suggest the possibility that the changes in the solubility and subcellular localization of the M protein determine the ability to produce cell-free progeny virus, at least to some extent, and play a role in the pathogenicity of variants causing SSPE.
Topics: Amino Acid Substitution; Animals; Cell Nucleus; Chlorocebus aethiops; Cytoplasm; Humans; Measles virus; Mutation, Missense; Point Mutation; Solubility; Subacute Sclerosing Panencephalitis; Vero Cells; Viral Proteins; Virus Replication
PubMed: 19397874
DOI: 10.1016/j.micinf.2009.01.009 -
MSphere Mar 2020Rory de Vries works in the field of viral pathogenesis and focuses on interactions between respiratory viruses (or corresponding vaccines) and the host immune system. In...
Rory de Vries works in the field of viral pathogenesis and focuses on interactions between respiratory viruses (or corresponding vaccines) and the host immune system. In this mSphere of Influence article, he reflects on how the articles "Predominant infection of CD150 lymphocytes and dendritic cells during measles virus infection of macaques" by R. L. de Swart et al. (R. L. de Swart, M. Ludlow, L. de Witte, Y. Yanagi, et al., PLoS Pathog 3:e178, 2007, https://doi.org/10.1371/journal.ppat.0030178) and "Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality" by M. J. Mina et al. (M. J. Mina, C. J. Metcalf, R. L. de Swart, A. D. M. E. Osterhaus, and B. T. Grenfell, Science 348:694-699, 2015, https://doi.org/10.1126/science.aaa3662) made an impact on him. These articles studied interactions between measles virus and the host and influenced him by making two important points. (i) It is crucial to use nonadapted (recombinant) viruses in disease-relevant model systems when studying virus-host interactions. (ii) Studying viral pathogenesis requires a combination of , , and studies, and a group of researchers with multiple expertises. He learned that only when all these aspects are combined, can one truly answer the question: "How does a virus cause disease?"
Topics: Host Microbial Interactions; Humans; Measles; Measles virus
PubMed: 32213621
DOI: 10.1128/mSphere.00105-20 -
Emerging Infectious Diseases Jul 2002Measles outbreaks in 1999 in Queensland and Victoria, Australia, were caused by a novel strain of clade G virus (proposed name g3). Epidemiologic and molecular evidence...
Measles outbreaks in 1999 in Queensland and Victoria, Australia, were caused by a novel strain of clade G virus (proposed name g3). Epidemiologic and molecular evidence supports independent circulation of this virus in Queensland, northern Australia, in addition to importation of the virus by East Timor refugees seeking safe haven in Australia.
Topics: Adult; Australia; Child; Emigration and Immigration; Evolution, Molecular; Female; Genes, Viral; Genotype; Humans; Indonesia; Male; Measles; Measles virus; Phylogeny; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Species Specificity; Time Factors
PubMed: 12095446
DOI: 10.3201/eid0807.010409 -
Japanese Journal of Infectious Diseases Nov 2018The incidence of modified measles (M-Me), characterized by milder symptoms than those of typical measles (T-Me), has been increasing in Japan. However, the outbreak...
The incidence of modified measles (M-Me), characterized by milder symptoms than those of typical measles (T-Me), has been increasing in Japan. However, the outbreak dominated by M-Me cases has not been thoroughly investigated worldwide. The largest importation-related outbreak of measles with genotype D8 occurred in Yamagata Prefecture, Japan, from March to April 2017. This phenomenon was observed after Japan had achieved measles elimination in 2015. We confirmed 60 cases by detecting the genome of the measles virus (MeV). Among the cases, 38 were M-Me and 22 were T-Me. Thirty-nine (65.0%) patients were 20-39 years of age. Three out of 7 primary cases produced 50 transmissions, of which each patient caused 9-25 transmissions. These patients were 22-31 years old and were not vaccinated. Moreover, they developed T-Me and kept contact with the public during their symptomatic periods. Considering that M-Me is generally caused by vaccine failure, some individuals in Japan may have insufficient immunity for MeV. Accordingly, additional doses of measles vaccine may be necessary in preventing measles importation and endemicity among individuals aged 20-39 years. Furthermore, to accurately and promptly diagnose individuals with measles, particularly those who can be considered as primary cases, efforts must be exerted to detect all measles cases using epidemiological and genetic approaches in countries where measles elimination had been achieved.
Topics: Adolescent; Adult; Child; Child, Preschool; Communicable Disease Control; Communicable Diseases, Imported; Disease Outbreaks; Disease Transmission, Infectious; Female; Genotype; Humans; Incidence; Infant; Japan; Male; Measles; Measles Vaccine; Measles virus; Middle Aged; Young Adult
PubMed: 29962488
DOI: 10.7883/yoken.JJID.2018.083 -
Viruses Apr 2017Although there have been many epidemiological reports of the inter-country transmission of measles, systematic analysis of the global transmission dynamics of the...
Although there have been many epidemiological reports of the inter-country transmission of measles, systematic analysis of the global transmission dynamics of the measles virus (MV) is limited. In this study, we applied phylogeographic analysis to characterize the global transmission dynamics of the MV using large-scale genetic sequence data (obtained for 7456 sequences) from 115 countries between 1954 and 2015. These analyses reveal the spatial and temporal characteristics of global transmission of the virus, especially in Australia, China, India, Japan, the UK, and the USA in the period since 1990. The transmission is frequently observed, not only within the same region but also among distant and frequently visited areas. Frequencies of export from measles-endemic countries, such as China, India, and Japan are high but decreasing, while the frequencies from countries where measles is no longer endemic, such as Australia, the UK, and the USA, are low but slightly increasing. The world is heading toward measles eradication, but the disease is still transmitted regionally and globally. Our analysis reveals that countries wherein measles is endemic and those having eliminated the disease (apart from occasional outbreaks) both remain a source of global transmission in this measles elimination era. It is therefore crucial to maintain vigilance in efforts to monitor and eradicate measles globally.
Topics: Disease Eradication; Disease Transmission, Infectious; Global Health; Humans; Measles; Measles virus; Molecular Epidemiology; Phylogeography; Spatio-Temporal Analysis; Topography, Medical
PubMed: 28420160
DOI: 10.3390/v9040082