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Journal of Medical Virology Feb 2022Measles is one of the most infectious diseases of humans. It is caused by the measles virus (MeV) and can lead to serious illness, lifelong complications, and even...
Measles is one of the most infectious diseases of humans. It is caused by the measles virus (MeV) and can lead to serious illness, lifelong complications, and even death. Whole-genome sequencing (WGS) is now available to study molecular epidemiology and identify MeV transmission pathways. In the present study, WGS of 23 MeV strains of genotype H1, collected in Mainland China between 2006 and 2018, were generated and compared to 31 WGSs from the public domain to analyze genomic characteristics, evolutionary rates and date of emergence of H1 genotype. The noncoding region between M and F protein genes (M/F NCR) was the most variable region throughout the genome. Although the nucleotide substitution rate of H1 WGS was around 0.75 × 10 substitution per site per year, the M/F NCR had an evolutionary rate three times higher, with 2.44 × 10 substitution per site per year. Phylogenetic analysis identified three distinct genetic groups. The Time of the Most Recent Common Ancestor (TMRCA) of H1 genotype was estimated at approximately 1988, while the first genetic group appeared around 1995 followed by two other genetic groups in 1999-2002. Bayesian skyline plot showed that the genetic diversity of the H1 genotype remained stable even though the number of MeV cases decreased 50 times between 2014 (52 628) and 2020 (993). The current coronavirus disease 2019 (COVID-19) pandemic might have some effect on the measles epidemic and further studies will be necessary to assess the genetic diversity of the H1 genotype in a post-COVID area.
Topics: China; Evolution, Molecular; Genes, Viral; Genetic Variation; Genome, Viral; Genomics; Genotype; Humans; Measles; Measles virus; Phylogeny; RNA, Viral
PubMed: 34761827
DOI: 10.1002/jmv.27448 -
The Journal of Infectious Diseases Feb 2021Measles virus (MeV) binds, infects, and kills CD150+ memory T cells, leading to immune amnesia. Whether MeV targets innate, memory-like T cells is unknown. We...
Measles virus (MeV) binds, infects, and kills CD150+ memory T cells, leading to immune amnesia. Whether MeV targets innate, memory-like T cells is unknown. We demonstrate that human peripheral blood and hepatic mucosa-associated invariant T (MAIT) cells and invariant natural killer T cells express surprisingly high levels of CD150, more than other lymphocyte subsets. Furthermore, exposing MAIT cells to MeV results in their efficient infection and rapid apoptosis. This constitutes the first report of direct MAIT cell infection by a viral pathogen. Given MAIT cells' antimicrobial properties, their elimination by MeV may contribute to measles-induced immunosuppression and heightened vulnerability to unrelated infections.
Topics: Apoptosis; Female; Humans; Interleukin-12; Interleukin-18; Leukocytes, Mononuclear; Male; Measles virus; Membrane Cofactor Protein; Mucosal-Associated Invariant T Cells; Natural Killer T-Cells; Signaling Lymphocytic Activation Molecule Family Member 1; T-Lymphocyte Subsets
PubMed: 32623457
DOI: 10.1093/infdis/jiaa407 -
Cancer Gene Therapy Jun 2023Self-replicating RNA viruses have been engineered as efficient expression vectors for vaccine development for infectious diseases and cancers. Moreover, self-replicating... (Review)
Review
Self-replicating RNA viruses have been engineered as efficient expression vectors for vaccine development for infectious diseases and cancers. Moreover, self-replicating RNA viral vectors, particularly oncolytic viruses, have been applied for cancer therapy and immunotherapy. Among negative strand RNA viruses, measles viruses and rhabdoviruses have been frequently applied for vaccine development against viruses such as Chikungunya virus, Lassa virus, Ebola virus, influenza virus, HIV, Zika virus, and coronaviruses. Immunization of rodents and primates has elicited strong neutralizing antibody responses and provided protection against lethal challenges with pathogenic viruses. Several clinical trials have been conducted. Ervebo, a vaccine based on a vesicular stomatitis virus (VSV) vector has been approved for immunization of humans against Ebola virus. Different types of cancers such as brain, breast, cervical, lung, leukemia/lymphoma, ovarian, prostate, pancreatic, and melanoma, have been the targets for cancer vaccine development, cancer gene therapy, and cancer immunotherapy. Administration of measles virus and VSV vectors have demonstrated immune responses, tumor regression, and tumor eradication in various animal models. A limited number of clinical trials have shown well-tolerated treatment, good safety profiles, and dose-dependent activity in cancer patients.
Topics: Male; Animals; Humans; RNA Viruses; Viruses; Neoplasms; RNA; Immunization; Genetic Vectors; Zika Virus; Zika Virus Infection
PubMed: 35169298
DOI: 10.1038/s41417-022-00436-7 -
Vaccine Oct 2023Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitos that causes a debilitating disease characterized by fever and long-lasting polyarthralgia. To date,...
Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitos that causes a debilitating disease characterized by fever and long-lasting polyarthralgia. To date, no vaccine has been licensed, but multiple vaccine candidates are under evaluation in clinical trials. One of these vaccines is based on a measles virus vector encoding for the CHIKV structural genes C, E3, E2, 6K, and E1 (MV-CHIK), which proved safe in phase I and II clinical trials and elicited CHIKV-specific antibody responses in adult measles seropositive vaccine recipients. Here, we predicted T-cell epitopes in the CHIKV structural genes and investigated whether MV-CHIK vaccination induced CHIKV-specific CD4 and/or CD8 T-cell responses. Immune-dominant regions containing multiple epitopes in silico predicted to bind to HLA class II molecules were found for four of the five structural proteins, while no such regions were predicted for HLA class I. Experimentally, CHIKV-specific CD4 T-cells were detected in six out of twelve participants after a single MV-CHIK vaccination and more robust responses were found 4 weeks after two vaccinations (ten out of twelve participants). T-cells were mainly directed against the three large structural proteins C, E2 and E1. Next, we sorted and expanded CHIKV-specific T cell clones (TCC) and identified human CHIKV T-cell epitopes by deconvolution. Interestingly, eight out of nine CD4 TCC recognized an epitope in accordance with the in silico prediction. CHIKV-specific CD8 T-cells induced by MV-CHIK vaccination were inconsistently detected. Our data show that the MV-CHIK vector vaccine induced a functional transgene-specific CD4 T cell response which, together with the evidence of neutralizing antibodies as correlate of protection for CHIKV, makes MV-CHIK a promising vaccine candidate in the prevention of chikungunya.
Topics: Adult; Humans; Antibodies, Neutralizing; Antibodies, Viral; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chikungunya Fever; Chikungunya virus; Epitopes, T-Lymphocyte; Measles Vaccine; Measles virus; Viral Vaccines
PubMed: 37726181
DOI: 10.1016/j.vaccine.2023.09.022 -
Global genetic diversity of measles virus (Paramyxoviridae: ): historical aspects and current state.Voprosy Virusologii Nov 2023Monitoring the circulation of the measles virus and studying its genetic diversity is an important component of the measles elimination program. A methodological... (Review)
Review
Monitoring the circulation of the measles virus and studying its genetic diversity is an important component of the measles elimination program. A methodological approach to molecular genetic studies and their interpretation in the measles surveillance was developed in the early 2000s. During its development, clear areas of circulation of each genotype of the virus were identified, therefore, the determination of viruses' genotypes was proposed to monitor circulation and identify transmission pathways. However, in the future, due to a significant decrease in the number of active genotypes, an approach based on sub-genotyping was proposed: determining not only the genotype of the virus, but also its genetic lineage/genetic variant. The Global Measles and Rubella Laboratory Network (GMRLN) systematically monitors the circulation of the measles virus at the sub-genotypic level, depositing the results in a specialized database MeaNS2. It is this database that is the most complete and reliable source of information about the genetic characteristic of measles viruses. This review presents both historical information and the latest data on the global genetic diversity of the measles virus.
Topics: Humans; Measles virus; Morbillivirus; Paramyxoviridae; Molecular Epidemiology; Measles; Genotype; Genetic Variation
PubMed: 38156571
DOI: 10.36233/0507-4088-187 -
Journal of Virology Jun 2021Measles virus (MeV), an enveloped RNA virus in the family , is still an important cause of childhood morbidity and mortality worldwide. MeV usually causes acute febrile...
Measles virus (MeV), an enveloped RNA virus in the family , is still an important cause of childhood morbidity and mortality worldwide. MeV usually causes acute febrile illness with skin rash, but in rare cases persists in the brain, causing a progressive neurological disorder, subacute sclerosing panencephalitis (SSPE). The disease is fatal, and no effective therapy is currently available. Although transsynaptic cell-to-cell transmission is thought to account for MeV propagation in the brain, neurons do not express the known receptors for MeV. Recent studies have shown that hyperfusogenic changes in the MeV fusion (F) protein play a key role in MeV propagation in the brain. However, how such mutant viruses spread in neurons remains unexplained. Here, we show that cell adhesion molecule 1 (CADM1; also known as IGSF4A, Necl-2, and SynCAM1) and CADM2 (also known as IGSF4D, Necl-3, SynCAM2) are host factors that enable MeV to cause membrane fusion in cells lacking the known receptors and to spread between neurons. During enveloped virus entry, a cellular receptor generally interacts in with the attachment protein on the envelope. However, CADM1 and CADM2 interact in with the MeV attachment protein on the same cell membrane, causing the fusion protein triggering and membrane fusion. Knockdown of CADM1 and CADM2 inhibits syncytium formation and virus transmission between neurons that are both mediated by hyperfusogenic F proteins. Thus, our results unravel the molecular mechanism (receptor-mimicking -acting fusion triggering) by which MeV spreads transsynaptically between neurons, thereby causing SSPE. Measles virus (MeV), an enveloped RNA virus, is the causative agent of measles, which is still an important cause of childhood morbidity and mortality worldwide. Persistent MeV infection in the brain causes a fatal progressive neurological disorder, subacute sclerosing panencephalitis (SSPE), several years after acute infection. However, how MeV spreads in neurons, which are mainly affected in SSPE, remains largely unknown. In this study, we demonstrate that cell adhesion molecule 1 (CADM1) and CADM2 are host factors enabling MeV spread between neurons. During enveloped virus entry, a cellular receptor generally interacts in with the attachment protein on the viral membrane (envelope). Remarkably, CADM1 and CADM2 interact in with the MeV attachment protein on the same membrane, triggering the fusion protein and causing membrane fusion, as viral receptors usually do in . Careful screening may lead to more examples of such "receptor-mimicking -acting fusion triggering" in other viruses.
Topics: Animals; Cell Adhesion Molecule-1; Cell Adhesion Molecules; Cell Line; Chlorocebus aethiops; Giant Cells; Humans; Measles virus; Mice; Subacute Sclerosing Panencephalitis; Vero Cells; Viral Envelope Proteins; Viral Fusion Proteins; Virus Internalization
PubMed: 33910952
DOI: 10.1128/JVI.00528-21 -
Methods in Molecular Biology (Clifton,... 2020With the recognition of oncolytic virotherapy as an immunotherapy, the distinct interactions between oncolytic agents and the immune system have come into focus. The...
With the recognition of oncolytic virotherapy as an immunotherapy, the distinct interactions between oncolytic agents and the immune system have come into focus. The role of the immune system in oncolytic virotherapy is somewhat ambiguous: While preexisting or arising immunity directed against viral antigens may preclude efficient viral replication and spread, immunity directed against tumor antigens is considered essential for long-term treatment success. Aside from the antiviral and antitumor immune status of the patient, the specific immunological microenvironment in a given tumor adds an additional layer of complexity.In this review we focus on the case of measles virus, which has long been known for its multifaceted interplay with the immune system. The high prevalence of measles-neutralizing antibodies in the general population may pose additional challenges. The oncolytic measles virus vector platform offers manifold opportunities for tumor-targeted immunomodulation. This review provides a survey of immunomodulation in the context of measles virotherapy including strategies to suppress or circumvent antiviral immunity as well as enhance antitumor immunity that have been pursued in preclinical and clinical studies. Understanding and selective manipulation of the intricate balance between antiviral and antitumor immunity will be crucial to develop the full potential of oncolytic virotherapy.
Topics: Animals; Biomarkers; Genetic Vectors; Host-Pathogen Interactions; Humans; Immunity; Immunomodulation; Immunotherapy; Measles virus; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Tumor Microenvironment; Virus Replication; Virus Shedding
PubMed: 31486034
DOI: 10.1007/978-1-4939-9794-7_7 -
Journal of Clinical Virology : the... Jul 2020Measles is a highly contagious viral illness that continues to cause significant mortality among young children worldwide despite the availability of a safe and... (Review)
Review
Measles is a highly contagious viral illness that continues to cause significant mortality among young children worldwide despite the availability of a safe and effective vaccine. During the first half of 2019, over 182 countries reported more than 300,000 measles cases; greater than double the number from the same period in 2018. Timely recognition and laboratory confirmation of infected individuals as well as appropriate infection prevention measures are crucial to avert further transmission. This review highlights the importance of early recognition of the signs and symptoms of measles and provides details on the laboratory methods commonly employed to confirm cases, investigate outbreaks and characterize the virus. It's critical that clinicians, laboratorians and public health administrations work together to rapidly identify, confirm and contain the spread of measles globally.
Topics: Child; Clinical Laboratory Techniques; Disease Outbreaks; Humans; Measles; Measles Vaccine; Measles virus; Vaccination
PubMed: 32454430
DOI: 10.1016/j.jcv.2020.104430 -
Expert Review of Vaccines Sep 2021The Development of the SARS-CoV-2 virus vaccine and its update on an ongoing pandemic is the first subject of the world health agenda.
INTRODUCTION
The Development of the SARS-CoV-2 virus vaccine and its update on an ongoing pandemic is the first subject of the world health agenda.
AREAS COVERED
First, we will scrutinize the biological features of the measles virus (MV), variola virus (smallpox virus), influenza virus, and their vaccines to compare them with the SARS-CoV-2 virus and vaccine. Next, we will discuss the statistical details of measuring the effectiveness of an improved vaccine.
EXPERT OPINION
Amidst the pandemic, we ought to acknowledge our prior experiences with respiratory viruses and vaccines. In the planning stage of observational Phase-III vaccine effectiveness studies, the sample size, sampling method, statistical model, and selection of variables are crucial in obtaining high-quality and valid results.
Topics: COVID-19; COVID-19 Vaccines; Humans; Immunity, Cellular; Influenza Vaccines; Mass Vaccination; Measles virus; Measles-Mumps-Rubella Vaccine; Orthomyxoviridae; SARS-CoV-2; Smallpox Vaccine; Vaccination; Vaccines, Attenuated; Variola virus
PubMed: 34365880
DOI: 10.1080/14760584.2021.1965884 -
Viruses Mar 2020Paramyxoviruses and pneumoviruses infect cells through fusion (F) protein-mediated merger of the viral envelope with target membranes. Members of these families include... (Review)
Review
Paramyxoviruses and pneumoviruses infect cells through fusion (F) protein-mediated merger of the viral envelope with target membranes. Members of these families include a range of major human and animal pathogens, such as respiratory syncytial virus (RSV), measles virus (MeV), human parainfluenza viruses (HPIVs), and highly pathogenic Nipah virus (NiV). High-resolution F protein structures in both the metastable pre- and the postfusion conformation have been solved for several members of the families and a number of F-targeting entry inhibitors have progressed to advanced development or clinical testing. However, small-molecule RSV entry inhibitors have overall disappointed in clinical trials and viral resistance developed rapidly in experimental settings and patients, raising the question of whether the available structural information may provide a path to counteract viral escape through proactive inhibitor engineering. This article will summarize current mechanistic insight into F-mediated membrane fusion and examine the contribution of structural information to the development of small-molecule F inhibitors. Implications are outlined for future drug target selection and rational drug engineering strategies.
Topics: Animals; Antiviral Agents; Binding Sites; Drug Discovery; Humans; Models, Molecular; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirus; Pneumovirus Infections; Protein Binding; Structure-Activity Relationship; Virus Internalization
PubMed: 32245118
DOI: 10.3390/v12030342