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Viruses Jul 2016Measles virus is a highly contagious negative strand RNA virus that is transmitted via the respiratory route and causes systemic disease in previously unexposed humans... (Review)
Review
Measles virus is a highly contagious negative strand RNA virus that is transmitted via the respiratory route and causes systemic disease in previously unexposed humans and non-human primates. Measles is characterised by fever and skin rash and usually associated with cough, coryza and conjunctivitis. A hallmark of measles is the transient immune suppression, leading to increased susceptibility to opportunistic infections. At the same time, the disease is paradoxically associated with induction of a robust virus-specific immune response, resulting in lifelong immunity to measles. Identification of CD150 and nectin-4 as cellular receptors for measles virus has led to new perspectives on tropism and pathogenesis. In vivo studies in non-human primates have shown that the virus initially infects CD150⁺ lymphocytes and dendritic cells, both in circulation and in lymphoid tissues, followed by virus transmission to nectin-4 expressing epithelial cells. The abilities of the virus to cause systemic infection, to transmit to numerous new hosts via droplets or aerosols and to suppress the host immune response for several months or even years after infection make measles a remarkable disease. This review briefly highlights current topics in studies of measles virus host invasion and pathogenesis.
Topics: Animals; Host-Pathogen Interactions; Humans; Measles virus; Primates
PubMed: 27483301
DOI: 10.3390/v8080210 -
Human Vaccines & Immunotherapeutics 2015Measles was an inevitable infection during the human development with substantial degree of morbidity and mortality. The severity of measles virus (MV) infection was... (Review)
Review
Measles was an inevitable infection during the human development with substantial degree of morbidity and mortality. The severity of measles virus (MV) infection was largely contained by the development of a live attenuated vaccine that was introduced into the vaccination programs. However, all efforts to eradicate the disease failed and continued to annually result in significant deaths. The development of molecular biology techniques allowed the rescue of MV from cDNA that enabled important insights into a variety of aspects of the biology of the virus and its pathogenesis. Subsequently these technologies facilitated the development of novel vaccine candidates that induce immunity against measles and other pathogens. Based on the promising prospective, the use of MV as a recombinant vaccine and a therapeutic vector is addressed.
Topics: Drug Carriers; Genetic Vectors; Humans; Measles; Measles Vaccine; Measles virus; Oncolytic Virotherapy; Vaccines, Attenuated; Vaccines, Synthetic
PubMed: 25483511
DOI: 10.4161/hv.34298 -
Current Opinion in Virology Feb 2021Effects of measles on the immune system are only partially understood. Lymphoid tissue is a primary site of measles virus (MeV) replication where CD150 is the receptor... (Review)
Review
Effects of measles on the immune system are only partially understood. Lymphoid tissue is a primary site of measles virus (MeV) replication where CD150 is the receptor for infection of both B and T cells. Lymphocyte depletion occurs during the acute phase of infection, but initiation of the adaptive immune response leads to extensive lymphocyte proliferation, production of MeV-specific antibody and T cells, the rash and clearance of infectious virus. Viral RNA persists in lymphoid tissue accompanied by ongoing germinal center proliferation, production of antibody-secreting cells, functionally distinct populations of T cells and antibody avidity maturation to establish life-long immunity. However, at the same time diversity of pre-existing antibodies and numbers of memory and naive B cells are reduced and susceptibility to other infections is increased.
Topics: Adaptive Immunity; Antibodies, Viral; Humans; Immune Tolerance; Immunity, Cellular; Lymphoid Tissue; Measles; Measles virus; Virus Replication
PubMed: 32891958
DOI: 10.1016/j.coviro.2020.08.002 -
Current Opinion in Virology Apr 2020Clearance of measles virus is complex. Infectious virus is cleared by the adaptive immune response manifested by the characteristic maculopapular rash. CD8 T cells are... (Review)
Review
Clearance of measles virus is complex. Infectious virus is cleared by the adaptive immune response manifested by the characteristic maculopapular rash. CD8 T cells are major effectors of infectious virus clearance, a process that may fail in individuals with compromised cellular immune responses leading to progressive giant cell pneumonia and/or measles inclusion body encephalitis. In contrast to the usual rapid clearance of infectious virus, clearance of viral RNA is slow with persistence in lymphoid tissue for many months. Persistence of MeV RNA may contribute to the late development of the slowly progressive disease subacute sclerosing panencephalitis in children infected at a young age and to measles-associated immune suppression but also to maturation of the immune response and development of life-long immunity.
Topics: Animals; CD8-Positive T-Lymphocytes; Humans; Measles; Measles virus; RNA, Viral
PubMed: 32387998
DOI: 10.1016/j.coviro.2020.03.003 -
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 -
Viruses Oct 2016Oncolytic virotherapeutic agents are likely to become serious contenders in cancer treatment. The vaccine strain of measles virus is an agent with an impressive range of... (Review)
Review
Oncolytic virotherapeutic agents are likely to become serious contenders in cancer treatment. The vaccine strain of measles virus is an agent with an impressive range of oncolytic activity in pre-clinical trials with increasing evidence of safety and efficacy in early clinical trials. This paramyxovirus vaccine has a proven safety record and is amenable to careful genetic modification in the laboratory. Overexpression of the measles virus (MV) receptor CD46 in many tumour cells may direct the virus to preferentially enter transformed cells and there is increasing awareness of the importance of nectin-4 and signaling lymphocytic activation molecule (SLAM) in oncolysis. Successful attempts to retarget MV by inserting genes for tumour-specific ligands to antigens such as carcinoembryonic antigen (CEA), CD20, CD38, and by engineering the virus to express synthetic microRNA targeting sequences, and "blinding" the virus to the natural viral receptors are exciting measures to increase viral specificity and enhance the oncolytic effect. Sodium iodine symporter (NIS) can also be expressed by MV, which enables in vivo tracking of MV infection. Radiovirotherapy using MV-NIS, chemo-virotherapy to convert prodrugs to their toxic metabolites, and immune-virotherapy including incorporating antibodies against immune checkpoint inhibitors can also increase the oncolytic potential. Anti-viral host immune responses are a recognized barrier to the success of MV, and approaches such as transporting MV to the tumour sites by carrier cells, are showing promise. MV Clinical trials are producing encouraging preliminary results in ovarian cancer, myeloma and cutaneous non-Hodgkin lymphoma, and the outcome of currently open trials in glioblastoma multiforme, mesothelioma and squamous cell carcinoma are eagerly anticipated.
Topics: Clinical Trials as Topic; Drug Discovery; Humans; Measles virus; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 27782084
DOI: 10.3390/v8100294 -
FEMS Microbiology Reviews May 2012Measles remains one of the most important causes of child morbidity and mortality worldwide with the greatest burden in the youngest children. Most acute measles deaths... (Review)
Review
Measles remains one of the most important causes of child morbidity and mortality worldwide with the greatest burden in the youngest children. Most acute measles deaths are owing to secondary infections that result from a poorly understood measles-induced suppression of immune responses. Young children are also vulnerable to late development of subacute sclerosing panencephalitis, a progressive, uniformly fatal neurologic disease caused by persistent measles virus (MeV) infection. During acute infection, the rash marks the appearance of the adaptive immune response and CD8(+) T cell-mediated clearance of infectious virus. However, after clearance of infectious virus, MeV RNA persists and can be detected in blood, respiratory secretions, urine, and lymphoid tissue for many weeks to months. This prolonged period of virus clearance may help to explain measles immunosuppression and the development of lifelong immunity to re-infection, as well as occasional infection of the nervous system. Once MeV infects neurons, the virus can spread trans-synaptically and the envelope proteins needed to form infectious virus are unnecessary, accumulate mutations, and can establish persistent infection. Identification of the immune mechanisms required for the clearance of MeV RNA from multiple sites will enlighten our understanding of the development of disease owing to persistent infection.
Topics: Animals; CD8-Positive T-Lymphocytes; Disease Models, Animal; Exanthema; Host-Pathogen Interactions; Humans; Immune Tolerance; Measles; Measles virus; RNA, Viral
PubMed: 22316382
DOI: 10.1111/j.1574-6976.2012.00330.x -
Current Cancer Drug Targets 2018Attenuated Edmonston lineage measles virus (MV-Edm) vaccine strains can preferentially infect and lyse a wide variety of cancer cells. Oncolytic MV-Edm derivatives are... (Review)
Review
Attenuated Edmonston lineage measles virus (MV-Edm) vaccine strains can preferentially infect and lyse a wide variety of cancer cells. Oncolytic MV-Edm derivatives are genetically engineered to express the human carcinoembryonic antigen (MV-CEA virus) or the human sodium iodide symporter (MV-NIS virus) and are currently being tested in clinical trials against ovarian cancer, glioblastoma multiforme, multiple myeloma, mesothelioma, head and neck cancer, breast cancer and malignant peripheral nerve sheath tumors. This review describes the basic and preclinical data that facilitated the clinical translation of MV-Edm strains, and summarizes the clinical results of this oncolytic platform to date. Furthermore, we discuss the latest clinically relevant MV-Edm vector developments and creative strategies for future translational steps.
Topics: Clinical Trials as Topic; Humans; Measles virus; Neoplasms; Oncolytic Virotherapy; Treatment Outcome
PubMed: 28228086
DOI: 10.2174/1568009617666170222125035 -
Viruses Nov 2016The measles virus (MeV) is a contagious pathogenic RNA virus of the family , genus , that can cause serious symptoms and even fetal complications. Here, we summarize... (Review)
Review
The measles virus (MeV) is a contagious pathogenic RNA virus of the family , genus , that can cause serious symptoms and even fetal complications. Here, we summarize current molecular advances in MeV research, and emphasize the connection between host cells and MeV replication. Although measles has reemerged recently, the potential for its eradication is promising with significant progress in our understanding of the molecular mechanisms of its replication and host-pathogen interactions.
Topics: Host-Pathogen Interactions; Humans; Immunity, Innate; Measles virus; Virus Replication
PubMed: 27854326
DOI: 10.3390/v8110308 -
Virus Research May 2019Measles virus (MeV) is an immunosuppressive, extremely contagious RNA virus that remains a leading cause of death among children. MeV is dual-tropic: it replicates first... (Review)
Review
Measles virus (MeV) is an immunosuppressive, extremely contagious RNA virus that remains a leading cause of death among children. MeV is dual-tropic: it replicates first in lymphatic tissue, causing immunosuppression, and then in epithelial cells of the upper airways, accounting for extremely efficient contagion. Efficient contagion is counter-intuitive because the enveloped MeV particles are large and relatively unstable. However, MeV particles can contain multiple genomes, which can code for proteins with different functional characteristics. These proteins can cooperate to promote virus spread in tissue culture, prompting the question of whether multi-genome MeV transmission may promote efficient MeV spread also in vivo. Consistent with this hypothesis, in well-differentiated primary human airway epithelia large genome populations spread rapidly through intercellular pores. In another line of research, it was shown that distinct lymphocytic-adapted and epithelial-adapted genome populations exist; cyclical adaptation studies indicate that suboptimal variants in one environment may constitute a low frequency reservoir for adaptation to the other environment. Altogether, these observations suggest that, in humans, MeV spread relies on en bloc genome transmission, and that genomic diversity is instrumental for rapid MeV dissemination within hosts.
Topics: Cells, Cultured; Epithelial Cells; Genetic Variation; Genome, Viral; Humans; Measles; Measles virus; Receptors, Virus; Respiratory Mucosa; Respiratory System; Virion; Virus Internalization
PubMed: 30853585
DOI: 10.1016/j.virusres.2019.03.007