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2.
Epidemics ; 46: 100751, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38442537

RESUMO

Mumps virus is a highly transmissible pathogen that is effectively controlled in countries with high vaccination coverage. Nevertheless, outbreaks have occurred worldwide over the past decades in vaccinated populations. Here we analyse an outbreak of mumps virus genotype G among college students in the Netherlands over the period 2009-2012 using paired serological data. To identify infections in the presence of preexisting antibodies we compared mumps specific serum IgG concentrations in two consecutive samples (n=746), whereby the first sample was taken when students started their study prior to the outbreaks, and the second sample was taken 2-5 years later. We fit a binary mixture model to the data. The two mixing distributions represent uninfected and infected classes. Throughout we assume that the infection probability increases with the ratio of antibody concentrations of the second to first sample. The estimated infection attack rate in this study is higher than reported earlier (0.095 versus 0.042). The analyses yield probabilistic classifications of participants, which are mostly quite precise owing to the high intraclass correlation of samples in uninfected participants (0.85, 95%CrI: 0.82-0.87). The estimated probability of infection increases with decreasing antibody concentration in the pre-outbreak sample, such that the probability of infection is 0.12 (95%CrI: 0.10-0.13) for the lowest quartile of the pre-outbreak samples and 0.056 (95%CrI: 0.044-0.068) for the highest quartile. We discuss the implications of these insights for the design of booster vaccination strategies.


Assuntos
Caxumba , Humanos , Caxumba/epidemiologia , Caxumba/prevenção & controle , Incidência , Vírus da Caxumba/genética , Surtos de Doenças/prevenção & controle , Estudantes
3.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(2): 225-229, 2024 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-38413061

RESUMO

Objective: To analyze the epidemic characteristics of mumps in people aged 0-14 years in Jiangxi Province and the vaccination situation of mumps-containing vaccines (including mumps vaccines) from 2015 to 2022 to provide a scientific basis for the prevention and control of mumps epidemic in Jiangxi Province. Methods: The mumps epidemic situation and mumps vaccination data in Jiangxi Province from 2015 to 2022 were obtained from Chinese Disease Prevention and Control Information System and Jiangxi Immunization Program Information System and were analyzed using descriptive epidemiological methods. The chi-square test, cluster analysis, and Cochran-Armitage trend test were used for statistical analysis. Results: From 2015 to 2022, a total of 40 734 cases of mumps were reported in people aged 0-14 in Jiangxi Province, with an annual average reported incidence rate of 53.69/100 000, and the peak of incidence occurred in aged 6-7 years group, and the reported incidence rate was 86.43/100 000. The high incidence seasons in 2015-2019 were summer and winter, and there was no significant high incidence season in 2020-2022. Mumps outbreaks mainly occurred in Shangrao, Ganzhou, and Ji'an, and the outbreak sites were mainly reported primary schools. From 2015 to 2019, the 1-year group was the primary age group for vaccination against mumps, while from 2020 to 2021, it was 0 and 1-year groups. Conclusions: From 2015 to 2022, the incidence of mumps in the population aged 0-14 in Jiangxi Province showed a downward trend, and the peak of incidence occurred in age group 6-7 years. It is suggested to continue to strengthen the coverage rate of 2 doses of mumps vaccination for school-age children and, simultaneously, strengthen the monitoring and prevention of mumps in key places to avoid outbreaks.


Assuntos
Caxumba , Criança , Humanos , Caxumba/epidemiologia , Caxumba/prevenção & controle , Vacina contra Caxumba , Vírus da Caxumba , Vacinação , Surtos de Doenças , Incidência , China/epidemiologia
4.
Hum Vaccin Immunother ; 20(1): 2302685, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38236022

RESUMO

Measles, mumps, and rubella (MMR) are highly infectious viral diseases affecting young children and have high secondary attack rates. Present MMR vaccines show consistent seroconversion rates for anti-measles and anti-rubella antibodies with variable responses for anti-mumps antibodies. Most common strains for MMR vaccines, currently available in India, are the Edmonston-Zagreb measles strain, Leningrad Zagreb (L-Z) mumps strain, and the RA 27/3 rubella strain. L-Z strain of mumps virus has been found to be associated with aseptic meningitis by different studies from different parts of the world including India. Recently, a novel freeze-dried MMR vaccine developed by Zydus Lifesciences (Zyvac MMR) contains Edmonston Zagreb measles strain, Hoshino mumps strain, and RA 27/3 rubella strain. The Hoshino strain is WHO approved and was found to induce interferon gamma production. This review article aims to provide a comprehensive appraisal of the data available on the safety and immunogenicity of the novel MMR vaccine.


Assuntos
Sarampo , Caxumba , Rubéola (Sarampo Alemão) , Criança , Humanos , Lactente , Pré-Escolar , Caxumba/prevenção & controle , Vacina contra Rubéola , Vacina contra Sarampo-Caxumba-Rubéola/efeitos adversos , Sarampo/prevenção & controle , Rubéola (Sarampo Alemão)/prevenção & controle , Vírus da Caxumba , Anticorpos Antivirais , Vacina contra Sarampo
5.
Vaccine ; 42(5): 1065-1070, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38092609

RESUMO

BACKGROUND: In France, mumps surveillance is conducted in primary care by the Sentinelles network, the National Reference Centre for Measles, Mumps and Rubella and Santé publique France. AIM: The objective of this study was to estimate the incidence of suspected mumps in general practice, the proportion of laboratory confirmed cases and the factors associated with a virological confirmation. METHODS: General practitioners (GPs) participating in the Sentinelles network should report all patients with suspected mumps according to a clinical definition in case of parotitis and a serological definition in case of clinical expression without parotitis. All suspected mumps cases reported between January 2014 and December 2020 were included. A sample of these cases were tested by real time reverse transcriptase polymerase chain reaction (RT-PCR) for mumps biological confirmation. RESULTS: A total of 252 individuals with suspected mumps were included in the study. The average annual incidence rate of suspected mumps in general practice in France between 2014 and 2020 was estimated at 11 cases per 100,000 population [CI95%: 6-17]. A mumps confirmation RT-PCR test was performed on 146 cases amongst which 17 (11.5 %) were positive. Age (between 20 and 29 years old), the presence of a clinical complication and an exposure to a suspected mumps case within the 21 days prior the current episode were associated with a mumps biological confirmation. CONCLUSION: If these results confirm the circulation of mumps virus in France, they highlight the limits of a surveillance without a systematic laboratory confirmation in highly immunized populations.


Assuntos
Medicina Geral , Caxumba , Parotidite , Humanos , Adulto Jovem , Adulto , Caxumba/diagnóstico , Caxumba/epidemiologia , Caxumba/prevenção & controle , Parotidite/epidemiologia , Vírus da Caxumba , França/epidemiologia , Vacina contra Sarampo-Caxumba-Rubéola
6.
PLoS One ; 18(12): e0295819, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38091318

RESUMO

New therapeutic approaches can significantly impact the control of colorectal cancer (CRC), which is increasing worldwide. In this study, we investigated the potential of targeting viral proteins to combat cancer cells. Specifically, we examined the anticancer potential of the matrix (M) protein of the mumps virus Hoshino strain in SW480 CRC cell lines. To begin, we individually transfected SW480 cells with pcDNA3 plasmids containing the mumps virus M gene. We then investigated the percentage of cell death, caspase activity, and the expression levels of genes involved in apoptosis pathways. Following this, we performed bioinformatics analysis on the M protein to identify any similarities with Bcl-2 family members and their viral homologs. Our diagnostic methods showed that treatment with the mumps M protein induced apoptosis and upregulated the expression and activity of pro-apoptotic proteins in SW480 CRC cells compared to the control and vector groups. Based on our bioinformatics studies, we proposed that the BH3 motif in the M protein may trigger apoptosis in CRC cells by interacting with cellular Bax. Overall, our study showed for the first time that the mumps virus M protein could be considered as a targeted treatment for CRC by inducing apoptotic pathways.


Assuntos
Neoplasias Colorretais , Vírus da Caxumba , Humanos , Vírus da Caxumba/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-bcl-2 , Apoptose/genética
7.
Viruses ; 15(12)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38140661

RESUMO

Mumps is a vaccine-preventable disease caused by the mumps virus (MuV). However, MuV has re-emerged in many countries with high vaccine coverage. The World Health Organization (WHO) recommends molecular surveillance based on sequencing of the small hydrophobic (SH) gene. Additionally, the combined use of SH and non-coding regions (NCR) has been described in different studies, proving to be a useful complement marker to discriminate general patterns of circulation at national and international levels. The aim of this work is to test local-level usefulness of the combination of SH and MF-NCR sequencing in tracing hidden transmission clusters and chains during the last epidemic wave (2015-2020) in Spain. A database with 903 cases from the Autonomous Community of Madrid was generated by the integration of microbiological and epidemiological data. Of these, 453 representative cases were genotyped. Eight different SH variants and thirty-four SH haplotypes were detected. Local MuV circulation showed the same temporal pattern previously described at a national level. Only two of the thirteen previously identified outbreaks were caused by more than one variant/haplotype. Geographical representation of SH variants allowed the identification of several previously undetected clusters, which were analysed phylogenetically by the combination of SH and MF-NCR, in a total of 90 cases. MF-NCR was not able to improve the discrimination of geographical clusters based on SH sequencing, showing limited resolution for outbreak investigations.


Assuntos
Vírus da Caxumba , Caxumba , Humanos , Vírus da Caxumba/genética , Filogenia , Caxumba/epidemiologia , Surtos de Doenças , Genótipo
8.
Vaccine ; 41(25): 3728-3739, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37169652

RESUMO

Although mumps vaccination has been routine in Canada for decades, mumps cases and outbreaks continue to occur periodically. Mumps surveillance, including monitoring of the mumps virus genotype associated with disease activity, is important to document baseline activity and to advance further research into vaccine effectiveness. Here we describe a detailed analysis of mumps cases that have been detected in Canada from 2002 to 2020, with a focus on the mumps molecular epidemiology. In total, 7395 cases of mumps were reported to the surveillance system, with outbreaks occurring in the years 2007, 2010 and 2016 to 2018. Adolescents and young adults aged 15 to 29 years had the highest risk of being a case (rate ratios ranging from 1.50 to 2.29), compared to adults aged 30 to 39. Genotypes of mumps viruses were determined in 3225 specimens. Genotype G was predominantly detected (96% of genotyped specimens) and was first reported in 2005. Other genotypes were more likely to be detected in cases that also reported travel (or were linked to imported cases) than the cases with genotype G detected (p < 0.0001). The genotype G viruses had little sequence diversity in the 316 nucleotide window used for genotyping (the small hydrophobic protein gene) and mainly belonged to a single phylogenetic lineage that included the MuVi/Sheffield.GBR/1.05 reference sequence. The analysis of over ten years of data has demonstrated that mumps genotype G, specifically belonging to a single lineage, the Sheffield lineage, is the endemically circulating virus in Canada. This lineage is seen also in other countries using the genotype A vaccine. Mumps remains endemic despite high MMR vaccination coverage which has been sufficient to eliminate circulation of measles and rubella in Canada, raising the hypothesis of the evolution towards a vaccine escape mumps virus.


Assuntos
Caxumba , Adolescente , Adulto Jovem , Humanos , Caxumba/epidemiologia , Caxumba/prevenção & controle , Filogenia , Vacina contra Sarampo-Caxumba-Rubéola , Vírus da Caxumba/genética , Canadá/epidemiologia , Surtos de Doenças/prevenção & controle
9.
Virus Genes ; 59(4): 515-523, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37133580

RESUMO

Mumps is a vaccine-preventable disease, and research on the vaccine's efficacy has recently indicated declining efficacy that has failed to protect against primary infections or reinfections, leading to a global resurgence in nations that use mumps vaccine in their national immunization programmes (NIPs). Lack of reports on its infection, documentation and published studies prevents it from being recognized as a public health issue in India. The waning of immunity is ascribed to the changes between the circulating and vaccine strains. The goal of the current study was to describe the circulating MuV strains in the Dibrugarh district of Assam, India, from 2016 to 2019. Blood samples were examined for IgM antibodies, and throat swab samples were put through Taqman assay for molecular detection. The small hydrophobic (SH) gene was targeted for genotyping through sequencing, and its genetic variations and phylogenetic analysis were carried out. Mumps RNA was found in 42 cases, and Mumps IgM in 14, of which 60% (25/42) of the cases were male and 40% (17/42) were female mostly affecting children between the ages of 6 and 12. Sequence and phylogeny analyses of SH gene revealed Genotypes C (83%) and G (17%) were simultaneously circulating during the study period. The study offers crucial genetic baseline information for the creation of Mumps prevention and control measures. Therefore, based on the research, it is clear that developing an effective vaccination strategy should take into account all currently prevalent genotypes in order to provide better protection against the disease's comeback.


Assuntos
Caxumba , Vacinas , Criança , Masculino , Humanos , Feminino , Vírus da Caxumba/genética , Caxumba/epidemiologia , Caxumba/prevenção & controle , Filogenia , RNA Viral/genética , Genótipo , Índia/epidemiologia , Imunoglobulina M
10.
Cell ; 186(9): 1877-1894.e27, 2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-37116470

RESUMO

Negative-stranded RNA viruses can establish long-term persistent infection in the form of large intracellular inclusions in the human host and cause chronic diseases. Here, we uncover how cellular stress disrupts the metastable host-virus equilibrium in persistent infection and induces viral replication in a culture model of mumps virus. Using a combination of cell biology, whole-cell proteomics, and cryo-electron tomography, we show that persistent viral replication factories are dynamic condensates and identify the largely disordered viral phosphoprotein as a driver of their assembly. Upon stress, increased phosphorylation of the phosphoprotein at its interaction interface with the viral polymerase coincides with the formation of a stable replication complex. By obtaining atomic models for the authentic mumps virus nucleocapsid, we elucidate a concomitant conformational change that exposes the viral genome to its replication machinery. These events constitute a stress-mediated switch within viral condensates that provide an environment to support upregulation of viral replication.


Assuntos
Vírus da Caxumba , Infecção Persistente , Humanos , Vírus da Caxumba/fisiologia , Nucleocapsídeo , Fosfoproteínas/metabolismo , Replicação Viral
11.
J Virol ; 97(4): e0035923, 2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-37017528

RESUMO

Mumps is a highly contagious viral disease that can be prevented by vaccination. In the last decade, we have encountered repeated outbreaks of mumps in highly vaccinated populations, which call into question the effectiveness of available vaccines. Animal models are crucial for understanding virus-host interactions, and viruses such as mumps virus (MuV), whose only natural host is the human, pose a particular challenge. In our study, we examined the interaction between MuV and the guinea pig. Our results present the first evidence that guinea pigs of the Hartley strain can be infected in vivo after intranasal and intratesticular inoculation. We observed a significant viral replication in infected tissues up to 5 days following infection and induction of cellular and humoral immune responses as well as histopathological changes in infected lungs and testicles, without clinical signs of disease. Transmission of the infection through direct contact between animals was not possible. Our results demonstrate that guinea pigs and guinea pig primary cell cultures represent a promising model for immunological and pathogenetic studies of the complex MuV infection. IMPORTANCE Understanding of mumps virus (MuV) pathogenesis and the immune responses against MuV infection is limited. One of the reasons is the lack of relevant animal models. This study explores the interaction between MuV and the guinea pig. We demonstrated that all tested guinea pig tissue homogenates and primary cell cultures are highly susceptible to MuV infection and that α2,3-sialylated glycans (MuV cellular receptors) are being abundantly expressed at their surface. The virus remains in the guinea pig lungs and trachea for up to 4 days following intranasal infection. Although asymptomatic, MuV infection strongly activates both humoral and cellular immune response in infected animals and provides protection against virus challenge. Infection of the lungs and testicles after intranasal and intratesticular inoculation, respectively, is also supported by histopathological changes in these organs. Our findings give perspective for application of guinea pigs in research on MuV pathogenesis, antiviral response, and vaccine development and testing.


Assuntos
Vírus da Caxumba , Caxumba , Animais , Cobaias , Humanos , Caxumba/imunologia , Caxumba/fisiopatologia , Caxumba/virologia , Vírus da Caxumba/metabolismo , Replicação Viral , Células Cultivadas , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Pulmão/virologia , Testículo/virologia
12.
J Med Virol ; 95(3): e28639, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36879533

RESUMO

Mumps is the second-most reported infectious disease in South Korea; however, due to the low pathogen confirmation rate in laboratory diagnoses, we proposed a method for reevaluating the high incidence rate via the laboratory verification of other viral diseases. In 2021, 63 cases of pharyngeal or cheek mucosal swabs of suspected mumps cases in Gwangju, South Korea, were assessed for causative pathogens using massive simultaneous pathogen testing. More than one respiratory virus was detected in 60 cases (95.2%), 44 (73.3%) of which were codetected. Human rhinovirus was detected in 47 cases, followed by human herpesvirus (HHV)6 in 30; HHV4 (17), human bocavirus (17), HHV5 (10), and human parainfluenza virus 3 (6) were also detected. Our findings suggest the need for further investigations on the pathogenesis of diseases mimicking mumps, which are considered to aid with appropriate public health responses, treatment, and the prevention of infectious disease outbreaks.


Assuntos
Herpesvirus Humano 6 , Bocavirus Humano , Caxumba , Viroses , Vírus , Humanos , Caxumba/diagnóstico , Caxumba/epidemiologia , Viroses/diagnóstico , Viroses/epidemiologia , República da Coreia/epidemiologia , Vírus da Caxumba
13.
Viruses ; 15(3)2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36992368

RESUMO

The importance of genomic surveillance on emerging diseases continues to be highlighted with the ongoing SARS-CoV-2 pandemic. Here, we present an analysis of a new bat-borne mumps virus (MuV) in a captive colony of lesser dawn bats (Eonycteris spelaea). This report describes an investigation of MuV-specific data originally collected as part of a longitudinal virome study of apparently healthy, captive lesser dawn bats in Southeast Asia (BioProject ID PRJNA561193) which was the first report of a MuV-like virus, named dawn bat paramyxovirus (DbPV), in bats outside of Africa. More in-depth analysis of these original RNA sequences in the current report reveals that the new DbPV genome shares only 86% amino acid identity with the RNA-dependent RNA polymerase of its closest relative, the African bat-borne mumps virus (AbMuV). While there is no obvious immediate cause for concern, it is important to continue investigating and monitoring bat-borne MuVs to determine the risk of human infection.


Assuntos
COVID-19 , Quirópteros , Animais , Humanos , Vírus da Caxumba/genética , Filogenia , SARS-CoV-2 , Genômica , Sudeste Asiático/epidemiologia , Paramyxoviridae/genética
14.
Vopr Virusol ; 68(1): 59-65, 2023 03 11.
Artigo em Russo | MEDLINE | ID: mdl-36961236

RESUMO

INTRODUCTION: Mumps is a viral infection of high social significance. National program Elimination of measles and rubella and achievement of a stable sporadic incidence of epidemic mumps in the Russian Federation (20212025) sets the aim of gradual integration of mumps surveillance into the existing measles and rubella surveillance system. One of the key components of surveillance system is a laboratory confirmation of mumps cases. There are two approaches for laboratory confirmation of mumps cases, based on serological or molecular genetic methods. The aim of the work is molecular genetic characteristic of the mumps viruses (MuVs) circulated in the Russian Federation in 2022. MATERIALS AND METHODS: Samples of swabs from the inner surface of the cheek of 11 patients with mumps were collected for the study. Viral RNA was isolated directly from the samples. The isolated RNA was used as a matrix for RT-PCR. PCR products were sequenced using the Sanger method, and phylogenetic analysis was performed using the MEGA-X software. RESULTS: The MuV genotype G was detected in all samples. Phylogenetic analysis showed the presence of two virus genetic groups G-1 and G-2 that were significantly different from the viruses circulating in other countries. CONCLUSION: The identification of two MuV genetic groups in a limited area suggests a high genetic diversity of the pathogen.


Assuntos
Sarampo , Caxumba , Rubéola (Sarampo Alemão) , Humanos , Vírus da Caxumba/genética , Caxumba/diagnóstico , Caxumba/epidemiologia , Paramyxoviridae , Genótipo , Filogenia , Sarampo/epidemiologia , Anticorpos Antivirais/genética
15.
Proc Natl Acad Sci U S A ; 120(3): e2207595120, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36623178

RESUMO

Over the past two decades, multiple countries with high vaccine coverage have experienced resurgent outbreaks of mumps. Worryingly, in these countries, a high proportion of cases have been among those who have completed the recommended vaccination schedule, raising alarm about the effectiveness of existing vaccines. Two putative mechanisms of vaccine failure have been proposed as driving observed trends: 1) gradual waning of vaccine-derived immunity (necessitating additional booster doses) and 2) the introduction of novel viral genotypes capable of evading vaccinal immunity. Focusing on the United States, we conduct statistical likelihood-based hypothesis testing using a mechanistic transmission model on age-structured epidemiological, demographic, and vaccine uptake time series data. We find that the data are most consistent with the waning hypothesis and estimate that 32.8% (32%, 33.5%) of individuals lose vaccine-derived immunity by age 18 y. Furthermore, we show using our transmission model how waning vaccine immunity reproduces qualitative and quantitatively consistent features of epidemiological data, namely 1) the shift in mumps incidence toward older individuals, 2) the recent recurrence of mumps outbreaks, and 3) the high proportion of mumps cases among previously vaccinated individuals.


Assuntos
Caxumba , Vacinas , Humanos , Estados Unidos/epidemiologia , Adolescente , Caxumba/epidemiologia , Caxumba/prevenção & controle , Funções Verossimilhança , Vírus da Caxumba/genética , Causalidade , Surtos de Doenças , Vacinação
16.
Virus Res ; 326: 199050, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36682462

RESUMO

Mumps virus is an infectious pathogen causing major health problems for humans such as encephalitis, orchitis, and parotitis. Therefore, designing an inhibitor for this virus is of great medical and public health importance. With this goal in mind, we investigate the affinity of different sialic acid-based compounds (ligands) against the hemagglutinin-neuraminidase (HN) protein of the mumps virus, using a combination of molecular dynamics (MD) simulations and quantum chemistry calculations. Our MD simulation results indicate that the ligands form stable complexes with the HN protein through a combination of electrostatic, van der Waals (vdW), and hydrogen bond (H-bond) interactions, which the electrostatic interactions play a more important role in the complexation process. Based on the obtained results from the structural analysis Arg381, Arg291, and Arg49 play a key role in the binding site interactions with the different ligands, in comparison with other residues. There are some candidates such as Neu5Acα2-6Galß1-4GlcNAcß, Neu5Acα2-3Galß1-3GlcNacß1-3Galß1-4Glc, and Neu5Acα2-6Galß1-4GlcNAcß1-3Galß1-4Glc that form more stable complexes with the HN than the α2-3-Sialyllactose confirmed by the calculated Gibbs binding energies (-39.65, -46.93, and -36.49 kcal.mol-1, respectively). To investigate the relationship between the molecular properties of the selected compounds and their affinity to the HN receptor, density functional theory dispersion corrected (DFT-D3) calculations were employed. According to our DFT-D3 results, neutral sialic acid-based compounds have lower reactivity to the mumps virus than the negativity charge structures. Moreover, by increasing the electronic chemical potential (µ) the vdW and H-bond interactions between drugs and the HN protein increase. In other words, by elevating the electron tendency of the selected ligands their affinity to the mumps virus increases. Our quantum chemistry calculations reveal that in addition to the structural features the molecular properties of the drugs can play important roles in their affinity and reactivity against the virus. The results of this study can provide useful details to design new compounds or improve their properties against the mumps virus.


Assuntos
Vírus da Caxumba , Ácido N-Acetilneuramínico , Humanos , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/metabolismo , Simulação de Dinâmica Molecular , Proteína HN/química , Ligantes , Proteínas Virais/metabolismo
17.
Microbiol Immunol ; 67(1): 44-47, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36259144

RESUMO

The reverse genetics system is a very powerful tool for analyzing the molecular mechanisms of viral propagation and pathogenesis. However, full-length genome plasmid construction is highly time-consuming and laborious, and undesired mutations may be introduced by Escherichia coli. This study shows a very rapid E. coli-free method of full-genome construction using the mumps virus as an example. This method was able to reduce dramatically the time for full-genome construction, which was used very efficiently for virus rescue, from several days or more to ~2 days, with a similar accuracy and yield to the conventional method using E. coli/plasmid.


Assuntos
Vírus da Caxumba , Genética Reversa , Vírus da Caxumba/genética , Genética Reversa/métodos , Plasmídeos/genética , Genoma Viral , Genes Virais , Escherichia coli/genética , Clonagem Molecular
18.
J Clin Virol ; 157: 105296, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36209622

RESUMO

BACKGROUND: Despite widespread use of the mumps vaccine resulting in significant reduction in the incidence of symptomatic mumps infection, large outbreaks continue to occur in highly vaccinated populations. OBJECTIVES: We examined the mumps-specific IgG, IgG subclasses and neutralization titres to the outbreak Genotype G5 and Jeryl Lynn vaccine (Genotype A) mumps strains. STUDY DESIGN: Sera from 207 individuals were classified into five distinct cohorts: healthy controls and mumps cases of 5-17 years and 18-25 years, and naturally infected individuals of 50+ years. Mumps specific IgG and IgG subclass levels were measured using modified ELISA assays with lysates and nucleoprotein antigens from both the mumps vaccine and circulating Genotype G5 strains. All sera were investigated for in vitro neutralizing antibody titres (GMT) using focus reduction neutralization assays. Data was analysed using the Kruskal-Wallis test and pairwise Wilcoxon tests. RESULTS: Mumps cases had higher mumps IgG levels compared to controls, to both the vaccine and outbreak strains, however levels decreased with age. Mumps IgG3 levels were significantly raised in mumps cases (p < 0.001). Neutralization titres were lower to the outbreak strain in all cohorts with titres markedly lower in the mumps cohorts compared to healthy controls. Mean GMT to the vaccine strain increased with age. The naturally infected group displayed the highest GMT to the JL vaccine and the lowest GMT to the outbreak strain. CONCLUSIONS: Antigenic differences between mumps vaccine strain and circulating mumps viruses decrease the cross-neutralization capacity of vaccine-induced antibodies which may play a role in breakthrough infection.


Assuntos
Caxumba , Humanos , Caxumba/epidemiologia , Caxumba/prevenção & controle , Vírus da Caxumba/genética , Vacina contra Caxumba , Anticorpos Antivirais , Testes de Neutralização , Imunoglobulina G , Surtos de Doenças
19.
Vaccine ; 40(44): 6397-6403, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-36184403

RESUMO

Mumps virus (MuV) is highly neurotropic and neurovirulent, hence, the neurovirulence of virus seeds used in the production of mumps vaccines must be tested. The previous neurovirulence evaluation method involves measuring the area of the cavity in the Lewis neonatal rat brain caused by MuV through paraffin sectioning and hematoxylin-eosin (HE) staining. However, the processes of paraffin sectioning and HE staining are time consuming and complicated. To solve this problem, in this study, a vibratome sectioning system was first deployed to evaluate MuV neurovirulence in the rat brain instead of paraffin sectioning and HE staining. The results showed that the vibratome sectioning method could assess the neurovirulence potential of MuV more objectively and efficiently. In addition, the effects of different MuV doses and the ages of the rats in days on this evaluation method were explored. The results indicate that MuV at no less than 10 50 % cell culture infective dose (CCID50) could cause obvious cavity formation in 1-day-old rat brains. The neonatal rat model developed in this study could evaluate the neurovirulence of different MuV strains with high sensitivity and good repeatability.


Assuntos
Vírus da Caxumba , Caxumba , Animais , Ratos , Ratos Wistar , Parafina , Amarelo de Eosina-(YS) , Hematoxilina , Ratos Endogâmicos Lew , Virulência , Vacina contra Caxumba
20.
J Virol ; 96(19): e0072222, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36135364

RESUMO

The nucleolus is the largest structure in the nucleus, and it plays roles in mediating cellular stress responses and regulating cell proliferation, as well as in ribosome biosynthesis. The nucleolus is composed of a variety of nucleolar factors that interact with each other in a complex manner to enable its function. Many viral proteins interact with nucleolar factors as well, affecting cellular morphology and function. Here, to investigate the association between mumps virus (MuV) infection and the nucleolus, we evaluated the necessity of nucleolar factors for MuV proliferation by performing a knockdown of these factors with small interfering (si)RNAs. Our results reveal that suppressing the expression of Treacle, which is required for ribosome biosynthesis, reduced the proliferative potential of MuV. Additionally, the one-step growth kinetics results indicate that Treacle knockdown did not affect the viral RNA and protein synthesis of MuV, but it did impair the production of infectious virus particles. Viral matrix protein (M) was considered a candidate Treacle interaction partner because it functions in the process of particle formation in the viral life cycle and is partially localized in the nucleolus. Our data confirm that MuV M can interact with Treacle and colocalize with it in the nucleolus. Furthermore, we found that viral infection induces relocalization of Treacle in the nucleus. Together, these findings suggest that interaction with Treacle in the nucleolus is important for the M protein to exert its functions late in the MuV life cycle. IMPORTANCE The nucleolus, which is the site of ribosome biosynthesis, is a target organelle for many viruses. It is increasingly evident that viruses can favor their own replication and multiplication by interacting with various nucleolar factors. In this study, we found that the nucleolar protein Treacle, known to function in the transcription and processing of pre-rRNA, is required for the efficient propagation of mumps virus (MuV). Specifically, our data indicate that Treacle is not involved in viral RNA or protein synthesis but is important in the processes leading to viral particle production in MuV infection. Additionally, we determined that MuV matrix protein (M), which functions mainly in viral particle assembly and budding, colocalized and interacted with Treacle. Furthermore, we found that Treacle is distributed throughout the nucleus in MuV-infected cells. Our research shows that the interaction between M and Treacle supports efficient viral growth in the late stage of MuV infection.


Assuntos
Vírus da Caxumba , Proteínas Nucleares , Proteínas da Matriz Viral , Nucléolo Celular/metabolismo , Humanos , Caxumba , Vírus da Caxumba/fisiologia , Proteínas Nucleares/metabolismo , Fosfoproteínas , Precursores de RNA/metabolismo , RNA Viral/metabolismo , Proteínas da Matriz Viral/metabolismo
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