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Cytokine & Growth Factor Reviews Dec 2020The study of measles virus (MeV) as a cancer immunotherapeutic was prompted by clinical observations of leukemia and lymphoma regressions in patients following measles... (Review)
Review
The study of measles virus (MeV) as a cancer immunotherapeutic was prompted by clinical observations of leukemia and lymphoma regressions in patients following measles virus infection in the 1970s and 1980s. Since then, numerous preclinical studies have confirmed the oncolytic activity of MeV vaccine strains as well as their potential to promote long-lasting tumor-specific immune responses. Early clinical data indicate that some of these effects may translate to the treatment of cancer patients. In this review, we provide a structured summary of current evidence for the anti-tumor immune activity of oncolytic MeV. We start with an overview of MeV oncolysis and MeV-induced immunogenic cell death. Next, we relate findings on MeV-mediated activation of antigen-presenting cells, T cell priming and effector mechanisms to the cancer immunity cycle. We discuss additional factors in the tumor microenvironment which are modulated by MeV treatment as well as the role of anti-viral immunity. Based on these findings, we highlight avenues for rational enhancement of oncolytic MeV immunotherapy by vector engineering. We further point to advantages and drawbacks of experimental models and propose areas warranting promising research. Lastly, we review the available immunomonitoring data from several Phase I clinical trials. While this review presents data for MeV, the concepts and principles introduced herein apply to other oncolytic viruses, providing a framework to assess novel cancer immunotherapies.
Topics: Humans; Immunotherapy; Measles Vaccine; Measles virus; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 32660751
DOI: 10.1016/j.cytogfr.2020.07.009 -
Viruses Jul 2019Epidemiological reports of phocine distemper virus (PDV) and cetacean morbillivirus (CeMV) have accumulated since their discovery nearly 30 years ago. In this review, we... (Review)
Review
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.
Topics: Animals; Caniformia; Cetacea; Distemper Virus, Phocine; Host Specificity; Lymphocyte Activation; Models, Molecular; Morbillivirus; Morbillivirus Infections; Phylogeny; Protein Conformation; Seawater; Signaling Lymphocytic Activation Molecule Family
PubMed: 31277275
DOI: 10.3390/v11070606 -
Current Opinion in Virology Feb 2016Morbilliviruses are pathogens of humans and other animals. Live attenuated morbillivirus vaccines have been used to end endemic transmission of measles virus (MV) in... (Review)
Review
Morbilliviruses are pathogens of humans and other animals. Live attenuated morbillivirus vaccines have been used to end endemic transmission of measles virus (MV) in many parts of the developed world and to eradicate rinderpest virus. Entry is mediated by two different receptors which govern virus lymphotropism and epitheliotropism. Morbillivirus transmissibility is unparalleled and MV represents the most infectious human pathogen on earth. Their evolutionary origins remain obscure and their potential for adaption to new hosts is poorly understood. It has been suggested that MV could be eradicated. Therefore it is imperative to dissect barriers which restrict cross species infections. This is important as ecological studies identify novel morbilliviruses in a vast number of small mammals and carnivorous predators.
Topics: Animals; Evolution, Molecular; Humans; Morbillivirus; Morbillivirus Infections; Zoonoses
PubMed: 26921570
DOI: 10.1016/j.coviro.2016.01.019 -
Current Opinion in Virology Apr 2020Measles caused an estimated minimum of one million fatalities annually before vaccination. Outstanding progress towards controlling the virus has been made since the... (Review)
Review
Measles caused an estimated minimum of one million fatalities annually before vaccination. Outstanding progress towards controlling the virus has been made since the measles vaccine was introduced, but reduction of measles case-fatalities has stalled at around 100,000 annually for the last decade and a 2019 resurgence in several geographical regions threatens some of these past accomplishments. Whereas measles eradication through vaccination is feasible, a potentially open-ended endgame of elimination may loom. Other than doubling-down on existing approaches, is it worthwhile to augment vaccination efforts with antiviral therapeutics to solve the conundrum? This question is hypothetical at present, since no drugs have yet been approved specifically for the treatment of measles, or infection by any other pathogen of the paramyxovirus family. This article will consider obstacles that have hampered anti-measles and anti-paramyxovirus drug development, discuss MeV-specific challenges of clinical testing, and define drug properties suitable to address some of these problems.
Topics: Animals; Antiviral Agents; Drug Development; Global Health; Humans; Measles; Measles Vaccine; Measles virus
PubMed: 32247280
DOI: 10.1016/j.coviro.2020.02.007 -
Emerging Infectious Diseases Jul 2021Morbilliviruses are highly contagious pathogens. The Morbillivirus genus includes measles virus, canine distemper virus (CDV), phocine distemper virus (PDV), peste des...
Morbilliviruses are highly contagious pathogens. The Morbillivirus genus includes measles virus, canine distemper virus (CDV), phocine distemper virus (PDV), peste des petits ruminants virus, rinderpest virus, and feline morbillivirus. We detected a novel porcine morbillivirus (PoMV) as a putative cause of fetal death, encephalitis, and placentitis among swine by using histopathology, metagenomic sequencing, and in situ hybridization. Phylogenetic analyses showed PoMV is most closely related to CDV (62.9% nt identities) and PDV (62.8% nt identities). We observed intranuclear inclusions in neurons and glial cells of swine fetuses with encephalitis. Cellular tropism is similar to other morbilliviruses, and PoMV viral RNA was detected in neurons, respiratory epithelium, and lymphocytes. This study provides fundamental knowledge concerning the pathology, genome composition, transmission, and cellular tropism of a novel pathogen within the genus Morbillivirus and opens the door to a new, applicable disease model to drive research forward.
Topics: Animals; Distemper Virus, Canine; Encephalitis; Fetal Death; Morbillivirus; Phylogeny; Swine
PubMed: 34152961
DOI: 10.3201/eid2707.203971 -
Viruses Sep 2016The morbillivirus genus comprises major human and animal pathogens, including the highly contagious measles virus. Morbilliviruses feature single stranded negative sense... (Review)
Review
The morbillivirus genus comprises major human and animal pathogens, including the highly contagious measles virus. Morbilliviruses feature single stranded negative sense RNA genomes that are wrapped by a plasma membrane-derived lipid envelope. Genomes are encapsidated by the viral nucleocapsid protein forming ribonucleoprotein complexes, and only the encapsidated RNA is transcribed and replicated by the viral RNA-dependent RNA polymerase (RdRp). In this review, we discuss recent breakthroughs towards the structural and functional understanding of the morbillivirus polymerase complex. Considering the clinical burden imposed by members of the morbillivirus genus, the development of novel antiviral therapeutics is urgently needed. The viral polymerase complex presents unique structural and enzymatic properties that can serve as attractive candidates for druggable targets. We evaluate distinct strategies for therapeutic intervention and examine how high-resolution insight into the organization of the polymerase complex may pave the path towards the structure-based design and optimization of next-generation RdRp inhibitors.
Topics: Animals; Antiviral Agents; Enzyme Inhibitors; Humans; Morbillivirus; RNA-Dependent RNA Polymerase
PubMed: 27626440
DOI: 10.3390/v8090251 -
Frontiers in Immunology 2019(CeMV; ) causes epizootic and interepizootic fatalities in odontocetes and mysticetes worldwide. Studies suggest there is different species-specific susceptibility to... (Comparative Study)
Comparative Study
(CeMV; ) causes epizootic and interepizootic fatalities in odontocetes and mysticetes worldwide. Studies suggest there is different species-specific susceptibility to CeMV infection, with striped dolphins (), bottlenose dolphins (), and Guiana dolphins () ranking among the most susceptible cetacean hosts. The pathogenesis of CeMV infection is not fully resolved. Since no previous studies have evaluated the organ-specific immunopathogenetic features of CeMV infection in tissues from infected dolphins, this study was aimed at characterizing and comparing immunophenotypic profiles of local immune responses in lymphoid organs (lymph nodes, spleen), lung and CNS in CeMV-molecularly (RT-PCR)-positive cetaceans from Western Mediterranean, Northeast-Central, and Southwestern Atlantic. Immunohistochemical (IHC) analyses targeted molecules of immunologic interest: caspase 3, CD3, CD20, CD57, CD68, FoxP3, MHCII, Iba1, IFNγ, IgG, IL4, IL10, lysozyme, TGFβ, and PAX5. We detected consistent CeMV-associated inflammatory response patterns. Within CNS, inflammation was dominated by CD3 (T cells), and CD20 and PAX5 (B cells) lymphocytes, accompanied by fewer Iba1, CD68, and lysozyme histiocytes, mainly in striped dolphins and bottlenose dolphins. Multicentric lymphoid depletion was characterized by reduced numbers of T cells and B cells, more pronounced in Guiana dolphins. Striped dolphins and bottlenose dolphins often had hyperplastic (regenerative) phenomena involving the aforementioned cell populations, particularly chronically infected animals. In the lung, there was mild to moderate increase in T cells, B cells, and histiocytes. Additionally, there was a generalized increased expression of caspase 3 in lymphoid, lung, and CNS tissues. Apoptosis, therefore, is believed to play a major role in generalized lymphoid depletion and likely overt immunosuppression during CeMV infection. No differences were detected regarding cytokine immunoreactivity in lymph nodes, spleen, and lung from infected and non-infected dolphins by semiquantitative analysis; however, there was striking immunoreactivity for IFNγ in the CNS of infected dolphins. These novel results set the basis for tissue-specific immunophenotypic responses during CeMV infection in three highly susceptible delphinid species. They also suggest a complex interplay between viral and host's immune factors, thereby contributing to gain valuable insights into similarities, and differences of CeMV infection's immunopathogenesis in relation to body tissues, CeMV strains, and cetacean hosts.
Topics: Animals; Atlantic Ocean; Central Nervous System; Cytokines; Dolphins; Female; Immunohistochemistry; Lung; Lymphoid Tissue; Male; Mediterranean Sea; Morbillivirus; Morbillivirus Infections; Paraffin Embedding; Species Specificity; Tissue Fixation
PubMed: 30936878
DOI: 10.3389/fimmu.2019.00485 -
Microbiology and Immunology Feb 2022Cetacean morbillivirus (CeMV) infects marine mammals often causing a fatal respiratory and neurological disease. Recently, CeMV has expanded its geographic and host... (Review)
Review
Cetacean morbillivirus (CeMV) infects marine mammals often causing a fatal respiratory and neurological disease. Recently, CeMV has expanded its geographic and host species range, with cases being reported worldwide among dolphins, whales, seals, and other aquatic mammalian species, and therefore has emerged as the most threatening nonanthropogenic factor affecting marine mammal's health and conservation. Extensive research efforts have aimed to understand CeMV epidemiology and ecology, however, the molecular mechanisms underlying its transmission and pathogenesis are still poorly understood. In particular, the field suffers from a knowledge gap on the structural and functional properties of CeMV proteins and their host interactors. Nevertheless, the body of scientific literature produced in recent years has inaugurated new investigational trends, driving future directions in CeMV molecular research. In this mini-review, the most recent literature has been summarized in the context of such research trends, and categorized into four priority research topics, such as (1) the interaction between CeMV glycoprotein and its host cell receptors across several species; (2) the CeMV molecular determinants responsible for different disease phenotype; (3) the host molecular determinants responsible for differential susceptibility to CeMV infection; (4) the CeMV molecular determinants responsible for difference virulence among circulating CeMV strains. Arguably, these are the most urgent topics that need to be investigated and that most promisingly will help to shed light on the details of CeMV evolutionary dynamics in the immediate future.
Topics: Animals; Cetacea; Morbillivirus; Morbillivirus Infections; Proteome
PubMed: 34779039
DOI: 10.1111/1348-0421.12949 -
Vaccine May 2014The impact of morbilliviruses on both human and animal populations is well documented in the history of mankind. Indeed, prior to the development of vaccines for these... (Review)
Review
The impact of morbilliviruses on both human and animal populations is well documented in the history of mankind. Indeed, prior to the development of vaccines for these diseases, morbilliviruses plagued both humans and their livestock that were heavily relied upon for food and motor power within communities. Measles virus (MeV) was responsible for the death of millions of people annually across the world and those fortunate enough to escape the disease often faced starvation where their livestock had died following infection with rinderpest virus (RPV) or peste des petits ruminants virus (PPRV). Canine distemper virus has affected dog populations for centuries and in the past few decades appears to have jumped species, now causing disease in a number of non-canid species, some of which are been pushed to the brink of extinction by the virus. During the age of vaccination, the introduction and successful application of vaccines against rinderpest and measles has led to the eradication of the former and the greater control of the latter. Vaccines against PPR and canine distemper have also been generated; however, the diseases still pose a threat to susceptible species. Here we review the currently available vaccines against these four morbilliviruses and discuss the prospects for the development of new generation vaccines.
Topics: Animals; Distemper Virus, Canine; Dogs; History, 20th Century; History, 21st Century; Humans; Measles virus; Morbillivirus; Morbillivirus Infections; Peste-des-petits-ruminants virus; Rinderpest virus; Ruminants; Vaccination; Vaccines, Attenuated; Vaccines, DNA; Viral Vaccines
PubMed: 24703852
DOI: 10.1016/j.vaccine.2014.03.053 -
Viruses Apr 2016Measles virus (MeV), a highly contagious member of the Paramyxoviridae family, causes measles in humans. The Paramyxoviridae family of negative single-stranded enveloped... (Review)
Review
Measles virus (MeV), a highly contagious member of the Paramyxoviridae family, causes measles in humans. The Paramyxoviridae family of negative single-stranded enveloped viruses includes several important human and animal pathogens, with MeV causing approximately 120,000 deaths annually. MeV and canine distemper virus (CDV)-mediated diseases can be prevented by vaccination. However, sub-optimal vaccine delivery continues to foster MeV outbreaks. Post-exposure prophylaxis with antivirals has been proposed as a novel strategy to complement vaccination programs by filling herd immunity gaps. Recent research has shown that membrane fusion induced by the morbillivirus glycoproteins is the first critical step for viral entry and infection, and determines cell pathology and disease outcome. Our molecular understanding of morbillivirus-associated membrane fusion has greatly progressed towards the feasibility to control this process by treating the fusion glycoprotein with inhibitory molecules. Current approaches to develop anti-membrane fusion drugs and our knowledge on drug resistance mechanisms strongly suggest that combined therapies will be a prerequisite. Thus, discovery of additional anti-fusion and/or anti-attachment protein small-molecule compounds may eventually translate into realistic therapeutic options.
Topics: Antiviral Agents; Binding Sites; Drug Discovery; Host-Pathogen Interactions; Humans; Measles; Measles virus; Models, Molecular; Protein Binding; Protein Conformation; Protein Folding; Protein Interaction Domains and Motifs; Protein Multimerization; Receptors, Virus; Structure-Activity Relationship; Viral Fusion Protein Inhibitors; Viral Fusion Proteins; Virus Internalization
PubMed: 27110811
DOI: 10.3390/v8040112