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Virology Journal Oct 2018Measles (MEV) and mumps virus (MUV) are enveloped, non-segmented, negative single stranded RNA viruses of the family Paramyxoviridae, and are the cause of measles and...
BACKGROUND
Measles (MEV) and mumps virus (MUV) are enveloped, non-segmented, negative single stranded RNA viruses of the family Paramyxoviridae, and are the cause of measles and mumps, respectively, both preventable by vaccination. Aside from proteins coded by the viral genome, viruses are considered to contain host cell proteins (HCPs). The presence of extracellular vesicles (ECVs), which are often co-purified with viruses due to their similarity in size, density and composition, also contributes to HCPs detected in virus preparations, and this has often been neglected. The aim was to identify which virus-coded proteins are present in MEV and MUV virions, and to try to detect which HCPs, if any, are incorporated inside the virions or adsorbed on their outer surface, and which are more likely to be a contamination from co-purified ECVs.
METHODS
MUV, MEV and ECVs were purified by ultracentrifugation, hydrophobic interaction chromatography and immunoaffinity chromatography, proteins in the samples were resolved by SDS-PAGE and subjected to identification by MALDI-TOF/TOF-MS. A comparative analysis of HCPs present in all samples was carried out.
RESULTS
By proteomics approach, it was verified that almost all virus-coded proteins are present in MEV and MUV particles. Protein C in MEV which was until now considered to be non-structural viral protein, was found to be present inside the MeV virions. Results on the presence of HCPs in differently purified virus preparations imply that actin, annexins, cyclophilin A, moesin and integrin β1 are part of the virions.
CONCLUSIONS
All HCPs detected in the viruses are present in ECVs as well, indicating their possible function in vesicle formation, or that most of them are only present in ECVs. Only five HCPs were constantly present in purified virus preparations, regardless of the purification method used, implying they are likely the integral part of the virions. The approach described here is helpful for further investigation of HCPs in other virus preparations.
Topics: Animals; Chlorocebus aethiops; Hydrophobic and Hydrophilic Interactions; Measles; Measles virus; Mumps; Mumps virus; Proteome; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Vero Cells; Viral Proteins; Virion
PubMed: 30326905
DOI: 10.1186/s12985-018-1073-9 -
Biological Chemistry Sep 2018In this review, we summarize the mechanisms by which sphingolipids modulate virus multiplication and the host innate immune response, using a number of host-virus... (Review)
Review
In this review, we summarize the mechanisms by which sphingolipids modulate virus multiplication and the host innate immune response, using a number of host-virus systems as illustrative models. Sphingolipids exert diverse functions, both at the level of the viral life cycle and in the regulation of antiviral immune responses. Sphingolipids may influence viral replication in three ways: by serving as (co)receptors during viral entry, by modulating virus replication, and by shaping the antiviral immune response. Several studies have demonstrated that sphingosine kinases (SphK) and their product, sphingosine-1-phosphate (S1P), enhance the replication of influenza, measles, and hepatitis B virus (HBV). In contrast, ceramides, particularly S1P and SphK1, influence the expression of type I interferon (IFN-I) by modulating upstream antiviral signaling and enhancing dendritic cell maturation, differentiation, and positioning in tissue. The synthetic molecule α-galactosylceramide has also been shown to stimulate natural killer cell activation and interferon (IFN)-γ secretion. However, to date, clinical trials have failed to demonstrate any clinical benefit for sphingolipids in the treatment of cancer or HBV infection. Taken together, these findings show that sphingolipids play an important and underappreciated role in the control of virus replication and the innate immune response.
Topics: Animals; Hepatitis B virus; Humans; Immunity, Innate; Measles virus; Orthomyxoviridae; Sphingolipids; Virus Replication
PubMed: 29975662
DOI: 10.1515/hsz-2018-0181 -
Current Opinion in Virology Feb 2020Vaccine-preventable diseases (VPD) including measles and mumps have been re-emerging in countries with sustained high vaccine coverage. For mumps, waning immunity has... (Review)
Review
Vaccine-preventable diseases (VPD) including measles and mumps have been re-emerging in countries with sustained high vaccine coverage. For mumps, waning immunity has been recognized as a major contributor to recent outbreaks. Although unvaccinated individuals account for most cases in recent measles outbreaks, the role of immune waning remains unclear. Accumulating serological and epidemiological evidence suggests that natural immunity induced by infection may be more durable compared to vaccine-induced immunity. As the proportion of population immunity via vaccination gradually increases and boosting through natural exposures becomes rare, risk of outbreaks may increase. Mechanistic insights into the coupled immuno-epidemiological dynamics of waning and boosting will be important to understand optimal vaccination strategies to combat VPD re-emergence and achieve eradication.
Topics: Animals; Humans; Measles; Measles Vaccine; Measles virus; Mumps; Mumps Vaccine; Mumps virus
PubMed: 32634672
DOI: 10.1016/j.coviro.2020.05.009 -
Journal of Medical Virology Jul 2022The measles virus (MV) remains a leading cause of morbidity and mortality in children under 5 years of age. Molecular identification of circulating wild-type MV) strains...
The measles virus (MV) remains a leading cause of morbidity and mortality in children under 5 years of age. Molecular identification of circulating wild-type MV) strains is a vital component of the measles elimination program. We received 159 oral swab samples from Afghanistan during 2008-2018. Viral RNA was extracted, followed by one-step RT-PCR and positive amplicons were subject to sequencing for genotype identification. Out of 159 total samples, 52% (83/159) were detected positive by RT-PCR. Genotype D4 was identified from 2.4% (2/83), genotype H1, 4.8% (4/83), and genotype B3, 92.7% (77/83) cases, respectively.
Topics: Afghanistan; Child; Child, Preschool; Genotype; Humans; Measles; Measles virus; Phylogeny; RNA, Viral
PubMed: 35261036
DOI: 10.1002/jmv.27707 -
Pathology Oncology Research : POR Oct 2016Evidence of an association between classical Hodgkin lymphoma and the measles virus has previously been presented by our group. Arguments held against our thesis were... (Review)
Review
Evidence of an association between classical Hodgkin lymphoma and the measles virus has previously been presented by our group. Arguments held against our thesis were reevaluated. Substantiation of a relationship between the measles virus and additional solid tumors was submitted. Moreover, a pathogenic pathway was suggested to support a possible contribution of the measles virus to the development of classical Hodgkin lymphoma. We have chosen to exclude a discussion of measles virotherapy, since this carries distinct implications. We now add new evidence regarding the expression of the measles virus phosphoprotein in a few cancers. We also suggest a role in this context for atypical measles syndrome in malignant tumors. Last, we propose a collaboration which may make the best, on the one hand of our cohort of classical Hodgkin lymphoma, half of which carry the measles virus expression in their tumor cells. The planned study will also look into the patients vaccination records and into a previous history of the measles disease. On the other hand, cohorts of patients diagnosed with late onset measles will be assessed for the eventual diagnosis of atypical measles syndrome and will be followed up for the subsequent development of a malignant tumor.
Topics: Animals; Humans; Measles; Measles virus; Neoplasms; Phosphoproteins; Viral Proteins
PubMed: 27287391
DOI: 10.1007/s12253-016-0080-7 -
Journal of Infection and Public Health Jun 2024Measles has been a significant public health concern in Pakistan, especially in the Khyber Pakhtunkhwa (KPK) province, where sporadic and silent epidemics continue to...
BACKGROUND
Measles has been a significant public health concern in Pakistan, especially in the Khyber Pakhtunkhwa (KPK) province, where sporadic and silent epidemics continue to challenge existing control measures. This study aimed to estimate the prevalence and investigate the molecular epidemiology of the measles virus (MeV) in KPK and explore the vaccination status among the suspected individuals.
METHODS
A cross-sectional study was conducted between February and October 2021. A total of 336 suspected measles cases from the study population were analyzed for IgM antibodies using Enzyme-Linked Immunosorbent Assay (ELISA). Throat swabs were randomly collected from a subset of positive cases for molecular analysis. Phylogenetic analysis of MeV isolates was performed using the neighbor-joining method. The vaccination status of individuals was also recorded.
RESULTS
Among the suspected participants, 61.0% (205/336) were ELISA positive for IgM antibodies, with a higher prevalence in males (64.17%) compared to females (57.04%). The majority of cases (36.0%) were observed in infants and toddlers, consistent with previous reports. The majority of IgM-positive cases (71.7%) had not received any dose of measles vaccine, highlighting gaps in vaccine coverage and the need for improved immunization programs. Genetic analysis revealed that all MeV isolates belonged to the B3 genotype, with minor genetic variations from previously reported variants in the region.
CONCLUSION
This study provides valuable insights into the genetic epidemiology of the MeV in KPK, Pakistan. The high incidence of measles infection among unvaccinated individuals highlights the urgency of raising awareness about vaccine importance and strengthening routine immunization programs.
Topics: Humans; Measles virus; Measles; Female; Male; Pakistan; Cross-Sectional Studies; Infant; Child, Preschool; Antibodies, Viral; Phylogeny; Immunoglobulin M; Child; Genotype; Adolescent; Adult; Enzyme-Linked Immunosorbent Assay; Measles Vaccine; Molecular Epidemiology; Young Adult; Prevalence; Seroepidemiologic Studies; Middle Aged
PubMed: 38636313
DOI: 10.1016/j.jiph.2024.03.028 -
Viruses May 2023Hepatocellular carcinoma (HCC) remains a difficult-to-treat cancer due to late diagnosis and limited curative treatment options. Developing more effective therapeutic...
Hepatocellular carcinoma (HCC) remains a difficult-to-treat cancer due to late diagnosis and limited curative treatment options. Developing more effective therapeutic strategies is essential for the management of HCC. Oncolytic virotherapy is a novel treatment modality for cancers, and its combination with small molecules merits further exploration. In this study, we combined oncolytic measles virus (MV) with the natural triterpenoid compound ursolic acid (UA) and evaluated their combination effect against HCC cells, including those harboring hepatitis B virus (HBV) or hepatitis C virus (HCV) replication. We found that the combination of MV and UA synergistically induced more cell death in Huh-7 HCC cells through enhanced apoptosis. In addition, increased oxidative stress and loss of mitochondrial potential were observed in the treated cells, indicating dysregulation of the mitochondria-dependent pathway. Similar synergistic cytotoxic effects were also found in HCC cells harboring HBV or HCV genomes. These findings underscore the potential of oncolytic MV and UA combination for further development as a treatment strategy for HCC.
Topics: Humans; Carcinoma, Hepatocellular; Oncolytic Viruses; Liver Neoplasms; Measles virus; Oncolytic Virotherapy; Antineoplastic Agents; Cell Line, Tumor; Hepatitis C; Ursolic Acid
PubMed: 37376594
DOI: 10.3390/v15061294 -
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 -
Croatian Medical Journal Oct 2022To determine the circulation patterns of measles virus in Bulgaria from 2012 to 2018 after a large measles outbreak in the country (2009-2011).
AIM
To determine the circulation patterns of measles virus in Bulgaria from 2012 to 2018 after a large measles outbreak in the country (2009-2011).
METHODS
Three types of clinical material were collected: serum samples, urine samples, and nasal swabs. Enzyme-linked immunosorbent assay (ELISA) was used to detect specific viral immunoglobulin (Ig) M/IgG antibodies. Viral RNA was extracted from all urine and nasal swabs.
RESULTS
In the investigated period, 102 patients were confirmed to have measles (age range: two months to 55 years). A total of 101 samples (99%) were measles-IgM positive. Most of them were detected in 2017 (73%, 74/101), when a measles outbreak in the country was reported. The majority of patients were unvaccinated children aged under 13 months. Out of 101 measles serum samples confirmed by ELISA, 18 (20.45%) were measles-IgG positive and 15 (17.05%) were borderline. Thirty-three positive PCR products were sequenced and genotyped. In 2013, 2016, 2017, and 2018, three different measles viral genotypes were detected: D8, H1, and B3. Most patients were unvaccinated or insufficiently vaccinated.
CONCLUSION
Preventive measures are indispensable to limit the infection in different regions of Bulgaria and its spread to other countries. As vaccination coverage against measles and other vaccine-preventable infections, including SARS-Co2, is low, it is necessary to perform molecular identification of viruses to monitor their circulation and pathogenicity.
Topics: Child; Humans; Infant; Measles virus; Bulgaria; Immunoglobulin M; Vaccination; Measles; Antibodies, Viral; Disease Outbreaks; Immunoglobulin G
PubMed: 36325672
DOI: 10.3325/cmj.2022.63.475 -
Viruses Aug 2016Globally eliminating measles using available vaccines is biologically feasible because the measles virus (MV) hemagglutinin (H) protein is antigenically stable. The H... (Review)
Review
Globally eliminating measles using available vaccines is biologically feasible because the measles virus (MV) hemagglutinin (H) protein is antigenically stable. The H protein is responsible for receptor binding, and is the main target of neutralizing antibodies. The immunodominant epitope, known as the hemagglutinating and noose epitope, is located near the receptor-binding site (RBS). The RBS also contains an immunodominant epitope. Loss of receptor binding correlates with an escape from the neutralization by antibodies that target the epitope at RBS. Another neutralizing epitope is located near RBS and is shielded by an N-linked sugar in certain genotype strains. However, human sera from vaccinees and measles patients neutralized all MV strains with similar efficiencies, regardless of the N-linked sugar modification or mutations at these epitopes. Two other major epitopes exist at a distance from RBS. One has an unstructured flexible domain with a linear neutralizing epitope. When MV-H forms a tetramer (dimer of dimers), these epitopes may form the dimer-dimer interface, and one of the two epitopes may also interact with the F protein. The neutralization mechanisms of antibodies that recognize these epitopes may involve inhibiting the H-F interaction or blocking the fusion cascade after MV-H binds to its receptors.
Topics: Antibodies, Neutralizing; Antibodies, Viral; Epitopes, B-Lymphocyte; Hemagglutinins, Viral; Humans; Measles virus
PubMed: 27490564
DOI: 10.3390/v8080216