-
Viruses Oct 2016Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying... (Comparative Study)
Comparative Study Review
Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development.
Topics: Animals; Disease Models, Animal; Distemper Virus, Canine; Dogs; Ferrets; Humans; Immune Evasion; Immune Tolerance; Measles virus; Viral Tropism
PubMed: 27727184
DOI: 10.3390/v8100274 -
Human Vaccines & Immunotherapeutics May 2016Attenuated measles virus (MV) is one of the most effective and safe vaccines available, making it attractive candidate vector to prevent infectious diseases. Attenuated... (Review)
Review
Attenuated measles virus (MV) is one of the most effective and safe vaccines available, making it attractive candidate vector to prevent infectious diseases. Attenuated MV have acquired the ability to use the complement regulator CD46 as a major receptor to mediate virus entry and intercellular fusion. Therefore, attenuated MV strains preferentially infect and destroy a wide variety of cancer cells making them also attractive oncolytic vectors. The use of recombinant MV vector has to comply with various regulatory requirements, particularly relating to the assessment of potential risks for human health and the environment. The present article highlights the main characteristics of MV and recombinant MV vectors used for vaccination and virotherapy and discusses these features from a biosafety point of view.
Topics: Animals; Containment of Biohazards; Genetic Vectors; Humans; Measles; Measles Vaccine; Measles virus; Membrane Cofactor Protein; Mice; Oncolytic Virotherapy; Vaccination; Vaccines, Attenuated; Virus Internalization
PubMed: 26631840
DOI: 10.1080/21645515.2015.1122146 -
Viruses Apr 2016Antigenic drift and genetic variation are significantly constrained in measles virus (MeV). Genetic stability of MeV is exceptionally high, both in the lab and in the... (Review)
Review
Antigenic drift and genetic variation are significantly constrained in measles virus (MeV). Genetic stability of MeV is exceptionally high, both in the lab and in the field, and few regions of the genome allow for rapid genetic change. The regions of the genome that are more tolerant of mutations (i.e., the untranslated regions and certain domains within the N, C, V, P, and M proteins) indicate genetic plasticity or structural flexibility in the encoded proteins. Our analysis reveals that strong constraints in the envelope proteins (F and H) allow for a single serotype despite known antigenic differences among its 24 genotypes. This review describes some of the many variables that limit the evolutionary rate of MeV. The high genomic stability of MeV appears to be a shared property of the Paramyxovirinae, suggesting a common mechanism that biologically restricts the rate of mutation.
Topics: Adaptation, Biological; Animals; Antigenic Variation; Genetic Variation; Genomic Instability; Genotype; Humans; Measles; Measles virus; Mutation; Open Reading Frames; Serogroup; Untranslated Regions; Viral Proteins
PubMed: 27110809
DOI: 10.3390/v8040109 -
The Journal of Infectious Diseases Jul 2011Recent progress in reducing global measles mortality has renewed interest in measles eradication. Three biological criteria are deemed important for disease eradication:... (Review)
Review
Recent progress in reducing global measles mortality has renewed interest in measles eradication. Three biological criteria are deemed important for disease eradication: (1) humans are the sole pathogen reservoir; (2) accurate diagnostic tests exist; and (3) an effective, practical intervention is available at reasonable cost. Interruption of transmission in large geographical areas for prolonged periods further supports the feasibility of eradication. Measles is thought by many experts to meet these criteria: no nonhuman reservoir is known to exist, accurate diagnostic tests are available, and attenuated measles vaccines are effective and immunogenic. Measles has been eliminated in large geographical areas, including the Americas. Measles eradication is biologically feasible. The challenges for measles eradication will be logistical, political, and financial.
Topics: Animals; Antibodies, Viral; Disease Reservoirs; Disease Susceptibility; Genetic Variation; Global Health; HIV Infections; Humans; Immunity, Maternally-Acquired; Infant; Measles; Measles Vaccine; Measles virus; Population Surveillance; Primate Diseases; Primates; RNA, Viral
PubMed: 21666201
DOI: 10.1093/infdis/jir065 -
Current Topics in Microbiology and... 2009Measles virus offers an ideal platform from which to build a new generation of safe, effective oncolytic viruses. Occasional so-called spontaneous tumor regressions have... (Clinical Trial)
Clinical Trial Review
Measles virus offers an ideal platform from which to build a new generation of safe, effective oncolytic viruses. Occasional so-called spontaneous tumor regressions have occurred during natural measles infections, but common tumors do not express SLAM, the wild-type MV receptor, and are therefore not susceptible to the virus. Serendipitously, attenuated vaccine strains of measles virus have adapted to use CD46, a regulator of complement activation that is expressed in higher abundance on human tumor cells than on their nontransformed counterparts. For this reason, attenuated measles viruses are potent and selective oncolytic agents showing impressive antitumor activity in mouse xenograft models. The viruses can be engineered to enhance their tumor specificity, increase their antitumor potency, and facilitate noninvasive in vivo monitoring of their spread. A major impediment to the successful deployment of oncolytic measles viruses as anticancer agents is the high prevalence of preexisting anti-measles immunity, which impedes bloodstream delivery and curtails intratumoral virus spread. It is hoped that these problems can be addressed by delivering the virus inside measles-infected cell carriers and/or by concomitant administration of immunosuppressive drugs. From a safety perspective, population immunity provides an excellent defense against measles spread from patient to carers and, in 50 years of human experience, reversion of attenuated measles to a wild-type pathogenic phenotype has not been observed. Clinical trials testing oncolytic measles viruses as an experimental cancer therapy are currently underway.
Topics: Animals; Genetic Engineering; Genetic Therapy; Genetic Vectors; Humans; Measles virus; Membrane Cofactor Protein; Mice; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 19203112
DOI: 10.1007/978-3-540-70617-5_11 -
Expert Opinion on Biological Therapy Mar 2017Oncolytic viruses represent a novel treatment modality that is unencumbered by the standard resistance mechanisms limiting the therapeutic efficacy of conventional... (Review)
Review
Oncolytic viruses represent a novel treatment modality that is unencumbered by the standard resistance mechanisms limiting the therapeutic efficacy of conventional antineoplastic agents. Attenuated engineered measles virus strains derived from the Edmonston vaccine lineage have undergone extensive preclinical evaluation with significant antitumor activity observed in a broad range of preclinical tumoral models. These have laid the foundation for several clinical trials in both solid and hematologic malignancies, which have demonstrated safety, biologic activity and the ability to elicit antitumor immune responses. Areas covered: This review examines the published preclinical data which supported the clinical translation of this therapeutic platform, reviews the available clinical trial data and expands on ongoing phase II testing. It also looks at approaches to optimize clinical applicability and offers future perspectives. Expert opinion: Reverse genetic engineering has allowed the generation of oncolytic MV strains retargeted to increase viral tumor specificity, or armed with therapeutic and immunomodulatory genes in order to enhance anti-tumor efficacy. Continuous efforts focusing on exploring methods to overcome resistance pathways and determining optimal combinatorial strategies will facilitate further development of this encouraging antitumor strategy.
Topics: Animals; Genetic Engineering; Humans; Measles virus; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 28129716
DOI: 10.1080/14712598.2017.1288713 -
Viruses Dec 2018The order harbors numerous viruses of significant relevance to human health, including both established and emerging infections. Currently, vaccines are only available... (Review)
Review
The order harbors numerous viruses of significant relevance to human health, including both established and emerging infections. Currently, vaccines are only available for a small subset of these viruses, and antiviral therapies remain limited. Being obligate cellular parasites, viruses must utilize the cellular machinery for their replication and spread. Therefore, targeting cellular pathways used by viruses can provide novel therapeutic approaches. One of the key challenges confronted by both hosts and viruses alike is the successful folding and maturation of proteins. In cells, this task is faced by cellular molecular chaperones, a group of conserved and abundant proteins that oversee protein folding and help maintain protein homeostasis. In this review, we summarize the current knowledge of how the interact with cellular chaperones, highlight key gaps in our knowledge, and discuss the potential of chaperone inhibitors as antivirals.
Topics: Antiviral Agents; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Host-Pathogen Interactions; Humans; Measles virus; Molecular Chaperones; Mononegavirales; Protein Folding; Respiratory Syncytial Viruses; Virus Replication
PubMed: 30544818
DOI: 10.3390/v10120699 -
Clinical Microbiology and Infection :... Aug 2017The WHO European Region (EUR) has adopted the goal of eliminating measles and rubella but individual countries perform differently in achieving this goal. Measles virus... (Review)
Review
BACKGROUND
The WHO European Region (EUR) has adopted the goal of eliminating measles and rubella but individual countries perform differently in achieving this goal. Measles virus spread across the EUR by mobile groups has recently led to large outbreaks in the insufficiently vaccinated resident population. As an instrument for monitoring the elimination process and verifying the interruption of endemic virus transmission, molecular surveillance has to provide valid and representative data. Irrespective of the country's specific situation, it is required to ensure the functionality of the laboratory surveillance that is supported by the WHO Global Measles and Rubella Laboratory Network.
AIMS
To investigate whether the molecular surveillance in the EUR is adequate for the challenges in the elimination phase, we addressed the quality assurance of molecular data, the continuity and intensity of molecular monitoring, and the analysis of transmission chains.
SOURCES
Published articles, the molecular External Quality Assessment Programme of the WHO, the Centralized Information System for Infectious Diseases of the WHO EUR and the WHO Measles and Rubella Nucleotide Surveillance databases served as information sources.
CONTENT
Molecular proficiency testing conducted by the WHO in 2016 has shown that the expertise for measles and rubella virus genotyping exists in all parts of the EUR. The analysis of surveillance data reported nationally to the WHO in 2013-2016 has revealed some countries with outbreaks but not sufficiently representative molecular data. Long-lasting supranational MV transmission chains were identified.
IMPLICATIONS
A more systematic molecular monitoring and recording of the transmission pattern for the whole EUR could help to create a meaningful picture of the elimination process.
Topics: Disease Outbreaks; Disease Transmission, Infectious; Epidemiological Monitoring; Europe; Genotyping Techniques; Humans; Laboratory Proficiency Testing; Measles; Measles virus; Molecular Epidemiology; Rubella; Rubella virus; World Health Organization
PubMed: 28712666
DOI: 10.1016/j.cmi.2017.06.030 -
PloS One 2009Measles is a highly contagious childhood disease associated with an immunological paradox: although a strong virus-specific immune response results in virus clearance...
Measles is a highly contagious childhood disease associated with an immunological paradox: although a strong virus-specific immune response results in virus clearance and the establishment of a life-long immunity, measles infection is followed by an acute and profound immunosuppression leading to an increased susceptibility to secondary infections and high infant mortality. In certain cases, measles is followed by fatal neurological complications. To elucidate measles immunopathology, we have analyzed the immune response to measles virus in mice transgenic for the measles virus receptor, human CD150. These animals are highly susceptible to intranasal infection with wild-type measles strains. Similarly to what has been observed in children with measles, infection of suckling transgenic mice leads to a robust activation of both T and B lymphocytes, generation of virus-specific cytotoxic T cells and antibody responses. Interestingly, Foxp3(+)CD25(+)CD4(+) regulatory T cells are highly enriched following infection, both in the periphery and in the brain, where the virus intensively replicates. Although specific anti-viral responses develop in spite of increased frequency of regulatory T cells, the capability of T lymphocytes to respond to virus-unrelated antigens was strongly suppressed. Infected adult CD150 transgenic mice crossed in an interferon receptor type I-deficient background develop generalized immunosuppression with an increased frequency of CD4(+)CD25(+)Foxp3(+) T cells and strong reduction of the hypersensitivity response. These results show that measles virus affects regulatory T-cell homeostasis and suggest that an interplay between virus-specific effector responses and regulatory T cells plays an important role in measles immunopathogenesis. A better understanding of the balance between measles-induced effector and regulatory T cells, both in the periphery and in the brain, may be of critical importance in the design of novel approaches for the prevention and treatment of measles pathology.
Topics: Animals; Brain; Forkhead Transcription Factors; Homeostasis; Immunity, Cellular; Measles; Measles virus; Mice; T-Cell Antigen Receptor Specificity; T-Lymphocytes, Regulatory
PubMed: 19319188
DOI: 10.1371/journal.pone.0004948 -
Current Opinion in Investigational... Aug 2009Infection by measles virus (MV) is a major cause of human morbidity and mortality worldwide. In 2001, the WHO, UNICEF and their partners launched the Measles Initiative,... (Review)
Review
Infection by measles virus (MV) is a major cause of human morbidity and mortality worldwide. In 2001, the WHO, UNICEF and their partners launched the Measles Initiative, the goals of which are to interrupt the transmission of MV in large geographic areas by increasing vaccination coverage and to assess the feasibility of eradicating MV worldwide. An estimated 74% reduction in mortality resulting from measles was achieved between 2000 and 2007, equivalent to a reduction of approximately 200,000 deaths annually. Despite this progress in the control of measles, the highest number of measles cases in more than a decade was observed in 2008 in several European countries and the US, and the virus was again declared endemic in the UK. In the light of this resurgence in the UK and the limitations associated with the current live-attenuated vaccine, this review discusses the means by which safe and effective measles antivirals could augment vaccination and strengthen global efforts to control measles. Important aspects of treatment are the potential to prevent infection effectively after exposure to MV, the improvement of case management, the amelioration of complications that frequently follow MV infection and the influence of antivirals on a potential strategy for global measles eradication.
Topics: Antiviral Agents; Disease Outbreaks; Humans; Measles; Measles Vaccine; Measles virus
PubMed: 19649926
DOI: No ID Found