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Science (New York, N.Y.) Jun 2020Many infectious diseases are thought to have emerged in humans after the Neolithic revolution. Although it is broadly accepted that this also applies to measles, the...
Many infectious diseases are thought to have emerged in humans after the Neolithic revolution. Although it is broadly accepted that this also applies to measles, the exact date of emergence for this disease is controversial. We sequenced the genome of a 1912 measles virus and used selection-aware molecular clock modeling to determine the divergence date of measles virus and rinderpest virus. This divergence date represents the earliest possible date for the establishment of measles in human populations. Our analyses show that the measles virus potentially arose as early as the sixth century BCE, possibly coinciding with the rise of large cities.
Topics: Cities; Communicable Diseases, Emerging; Evolution, Molecular; Genetic Variation; History, Ancient; Humans; Measles; Measles virus; Rinderpest virus
PubMed: 32554594
DOI: 10.1126/science.aba9411 -
Nature Communications Jan 2024Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in...
Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B. Primary endpoint was safety and toxicity: treatment was well tolerated with no dose-limiting toxicity being observed up to the maximum feasible dose (2×10 TCID50). Median OS, a secondary endpoint, was 11.6 mo and one year survival was 45.5% comparing favorably with contemporary controls. Other secondary endpoints included assessment of viremia, MV replication and shedding, humoral and cellular immune response to the injected virus. A 22 interferon stimulated gene (ISG) diagonal linear discriminate analysis (DLDA) classification algorithm in a post-hoc analysis was found to be inversely (R = -0.6, p = 0.04) correlated with viral replication and tumor microenvironment remodeling including proinflammatory changes and CD8 + T cell infiltration in post treatment samples. This data supports that oncolytic MV derivatives warrant further clinical investigation and that an ISG-based DLDA algorithm can provide the basis for treatment personalization.
Topics: Humans; Oncolytic Viruses; Measles virus; Glioblastoma; Carcinoembryonic Antigen; Oncolytic Virotherapy; Neoplasm Recurrence, Local; Measles Vaccine; Tumor Microenvironment
PubMed: 38216554
DOI: 10.1038/s41467-023-43076-7 -
Human Vaccines & Immunotherapeutics Nov 2022As measles vaccination coverage has increased, measles infection has shifted to the population of infants. We conducted a follow-up seroepidemiological study among...
BACKGROUND
As measles vaccination coverage has increased, measles infection has shifted to the population of infants. We conducted a follow-up seroepidemiological study among mothers and their infants to evaluate measles seroprevalence and the persistence of maternal measles antibody in Shufu, Kashgar from 2018 to 2020.
METHODS
Maternal venous blood and cord blood was obtained among mothers and their infants at 0, 3, 5, 8, 9, and 12 months of age. An enzyme-linked immunosorbent assay was used for quantitative measurement of measles antibodies. We analyzed the correlation between maternal and neonatal measles antibodies, and antibodies persistence after infants were born.
RESULTS
The overall neonatal maternal ratio was 2.38 (95%CI: 2.05-2.71). The measles antibodies for mothers and newborns were 438.93 IU/mL (95%CI: 409.47-470.51 IU/mL) and 440.10 IU/mL (95%CI: 410.82-471.48 IU/mL), respectively. Neonatal measles antibodies were dropping after birth and then beginning to increase starting at 8 months of age.
CONCLUSIONS
Infant measles antibody levels progressively declined after birth regardless of maternal measles antibody levels. Efforts should be carried out to eliminate measles.
Topics: Infant; Female; Infant, Newborn; Humans; Measles virus; Seroepidemiologic Studies; Measles; Antibodies, Viral; Enzyme-Linked Immunosorbent Assay; Measles Vaccine; Immunity, Maternally-Acquired
PubMed: 36399713
DOI: 10.1080/21645515.2022.2045854 -
Biomedica : Revista Del Instituto... Apr 2017Introducción. El virus del Zika (ZIKV) es un flavivirus con envoltura, transmitido a los seres humanos principalmente por el vector Aedes aegypti. La infección por...
Introducción. El virus del Zika (ZIKV) es un flavivirus con envoltura, transmitido a los seres humanos principalmente por el vector Aedes aegypti. La infección por ZIKV se ha asociado con un gran neurotropismo y con efectos neuropáticos, como el síndrome de Guillain-Barré en el adulto y la microcefalia fetal y posnatal, así como con un síndrome de infección congénita similar al producido por el virus de la rubéola (RV).Objetivo. Comparar las estructuras moleculares de la proteína de envoltura E del virus del Zika (E-ZIKV) y de la E1 del virus de la rubéola (E1-RV), y plantear posibles implicaciones en el neurotropismo y en las alteraciones del sistema nervioso asociadas con el ZIKV.Materiales y métodos. La secuencia de aminoácidos de la proteína E-ZIKV (PDB: 5iZ7) se alineó con la de la glucopreteína E1 del virus de la rubéola (PDB: 4ADG). Los elementos de la estructura secundaria se determinaron usando los programas Vector NTI Advance®, DSSP y POSA, así como herramientas de gestión de datos (AlignX®). Uno de los criterios principales de comparación y alineación fue la asignación de residuos estructuralmente equivalentes, con más de 70 % de identidad.Resultados. La organización estructural de la proteína E-ZIKV (PDB: 5iZ7) fue similar a la de E1-RV (PDB: 4ADG) (70 a 80 % de identidad), y se observó una correspondencia con la estructura definida para las glucoproteínas de fusión de membrana de clase II de los virus con envoltura. E-ZIKV y E1-RV exhibieron elementos estructurales de fusión muy conservados en la región distal del dominio II, asociados con la unión a los receptores celulares de entrada del virus de la rubéola (glucoproteína de mielina del oligodendrocito, Myelin Oligodendrocyte Glycoprotein, MOG), y con los receptores celulares Axl del ZIKV y de otros flavivirus.Conclusión. La comparación de las proteínas E-ZIKV y E1-RV es un paso necesario hacia la definición de otros factores moleculares determinantes del neurotropismo y la patogenia del ZIKV, el cual puede contribuir a generar estrategias de diagnóstico, prevención y tratamiento de las complicaciones neurológicas inducidas por el ZIKV.
Topics: Humans; Measles virus; Molecular Biology; Serine Endopeptidases; Viral Envelope Proteins; Viral Proteins; Zika Virus
PubMed: 28527274
DOI: 10.7705/biomedica.v37i0.3807 -
Viruses Oct 2022We investigated the epidemiology of measles and rubella infections in Senegal based on data from twelve consecutive years of laboratory-based surveillance (2010−2021)...
We investigated the epidemiology of measles and rubella infections in Senegal based on data from twelve consecutive years of laboratory-based surveillance (2010−2021) and conducted phylogenetic analyses of circulating measles viruses. Sera from measles-suspected cases were collected and tested for measles and rubella-specific IgM antibodies using enzyme-linked immunosorbent assays (ELISA). Throat swabs were collected from patients with clinically diagnosed measles for confirmation by reverse-transcription polymerase chain reaction (RT-PCR) and viral genotyping. Among 8082 laboratory-tested specimens from measles-suspected cases, serological evidence of measles and rubella infection was confirmed in 1303/8082 (16.1%) and 465/6714 (6.9%), respectively. The incidence of rubella is now low—0.8 (95% CI 0.4−1.3) cases per million people in 2021—whereas progress towards measles pre-elimination targets (<1.0 case per million people per year) appears to have stalled; there were 10.8 (95% CI 9.3−12.5) cases per million people in 2021. Phylogenetic analyses revealed that all Senegalese measles strains belonged to genotype B3. The rubella virus sequence obtained in this study was consistent with genotype 1C. Our national surveillance data suggest that despite their low incidence both measles and rubella remain endemic in Senegal with a concerning stagnation in the decline of measles infections that represents a significant challenge to the goal of regional elimination.
Topics: Humans; Molecular Epidemiology; Phylogeny; Incidence; Senegal; Rubella; Measles; Rubella virus; Measles virus; Antibodies, Viral; Genotype; Immunoglobulin M
PubMed: 36298828
DOI: 10.3390/v14102273 -
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 -
FEBS Letters Sep 2015In this review I summarize available data pointing to the abundance of structural disorder within the nucleoprotein (N) from three paramyxoviruses, namely the measles... (Review)
Review
In this review I summarize available data pointing to the abundance of structural disorder within the nucleoprotein (N) from three paramyxoviruses, namely the measles (MeV), Nipah (NiV) and Hendra (HeV) viruses. I provide a detailed description of the molecular mechanisms that govern the disorder-to-order transition that the intrinsically disordered C-terminal domain (NTAIL) of their N proteins undergoes upon binding to the C-terminal X domain (XD) of the homologous phosphoproteins. I also show that a significant flexibility persists within NTAIL-XD complexes, which makes them illustrative examples of "fuzziness". Finally, I discuss the functional implications of structural disorder for viral transcription and replication in light of the promiscuity of disordered regions and of the considerable reach they confer to the components of the replicative machinery.
Topics: Hendra Virus; Intrinsically Disordered Proteins; Measles virus; Models, Molecular; Nipah Virus; Nucleocapsid Proteins; Pliability; Protein Binding; Protein Folding; Protein Structure, Tertiary
PubMed: 26071376
DOI: 10.1016/j.febslet.2015.05.055 -
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 -
Nature Communications Apr 2018Measles virus (MeV) remains a major human pathogen, but there are presently no licensed antivirals to treat MeV or other paramyxoviruses. Here, we use cryo-electron...
Measles virus (MeV) remains a major human pathogen, but there are presently no licensed antivirals to treat MeV or other paramyxoviruses. Here, we use cryo-electron tomography (cryo-ET) to elucidate the principles governing paramyxovirus assembly in MeV-infected human cells. The three-dimensional (3D) arrangement of the MeV structural proteins including the surface glycoproteins (F and H), matrix protein (M), and the ribonucleoprotein complex (RNP) are characterized at stages of virus assembly and budding, and in released virus particles. The M protein is observed as an organized two-dimensional (2D) paracrystalline array associated with the membrane. A two-layered F-M lattice is revealed suggesting that interactions between F and M may coordinate processes essential for MeV assembly. The RNP complex remains associated with and in close proximity to the M lattice. In this model, the M lattice facilitates the well-ordered incorporation and concentration of the surface glycoproteins and the RNP at sites of virus assembly.
Topics: Cell Line; Cryoelectron Microscopy; Fibroblasts; HeLa Cells; Hemagglutinins, Viral; Humans; Measles virus; Ribonucleoproteins; Viral Fusion Proteins; Viral Matrix Proteins; Virion; Virus Assembly; Virus Release
PubMed: 29712906
DOI: 10.1038/s41467-018-04058-2