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Cell Apr 2023Negative-stranded RNA viruses can establish long-term persistent infection in the form of large intracellular inclusions in the human host and cause chronic diseases....
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.
Topics: Humans; Mumps virus; Nucleocapsid; Persistent Infection; Phosphoproteins; Virus Replication
PubMed: 37116470
DOI: 10.1016/j.cell.2023.03.015 -
Lancet (London, England) Mar 2008Mumps is a common childhood infection caused by the mumps virus. The hallmark of infection is swelling of the parotid gland. Aseptic meningitis and encephalitis are... (Review)
Review
Mumps is a common childhood infection caused by the mumps virus. The hallmark of infection is swelling of the parotid gland. Aseptic meningitis and encephalitis are common complications of mumps together with orchitis and oophoritis, which can arise in adult men and women, respectively; other complications include deafness and pancreatitis. Clinical diagnosis can be based on the classic parotid swelling; however, this feature is not present in all cases of mumps and can also occur in various other disorders. Laboratory diagnosis is based on isolation of virus, detection of viral nucleic acid, or serological confirmation (generally presence of IgM mumps antibodies). Mumps is vaccine-preventable, and one dose of mumps vaccine is about 80% effective against the disease. Routine vaccination has proven highly effective in reducing the incidence of mumps, and is presently used by most developed countries; however, there have been outbreaks of disease in vaccinated populations. In 2005, a large epidemic peaked in the UK, and in 2006 the American midwest had several outbreaks. In both countries, the largest proportion of cases was in young adults. In the UK, susceptible cohorts too old to have been vaccinated and too young to have been exposed to natural infections were the primary cause of the mumps epidemic. In the USA, effectiveness and uptake in combination appear not to have been sufficient to obtain herd immunity for mumps in populations such as college students.
Topics: Adult; Child, Preschool; Female; Humans; Male; Mumps; Mumps Vaccine; Mumps virus; Orchitis; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 18342688
DOI: 10.1016/S0140-6736(08)60419-5 -
Viruses Sep 2021Mumps virus (MuV) is an important human pathogen that causes parotitis, orchitis, oophoritis, meningitis, encephalitis, and sensorineural hearing loss. Although mumps is... (Review)
Review
Mumps virus (MuV) is an important human pathogen that causes parotitis, orchitis, oophoritis, meningitis, encephalitis, and sensorineural hearing loss. Although mumps is a vaccine-preventable disease, sporadic outbreaks have occurred worldwide, even in highly vaccinated populations. MuV not only causes systemic infection but also has a unique tropism to glandular tissues and the central nervous system. In general, tropism can be defined by multiple factors in the viral life cycle, including its entry, interaction with host factors, and host-cell immune responses. Although the underlying mechanisms of MuV tropism remain to be fully understood, recent studies on virus-host interactions have provided insights into viral pathogenesis. This review was aimed at summarizing the entry process of MuV by focusing on the glycan receptors, particularly the recently identified receptors with a trisaccharide core motif, and their interactions with the viral attachment proteins. Here, we describe the receptor structures, their distribution in the human body, and the recently identified host factors for MuV and analyze their relationship with MuV tropism.
Topics: Host-Pathogen Interactions; Humans; Mumps; Mumps virus; Protein Binding; Receptors, Virus; Viral Proteins; Viral Tropism; Virus Attachment; Virus Internalization
PubMed: 34578327
DOI: 10.3390/v13091746 -
Lancet (London, England) Feb 1947
Topics: Humans; Mumps virus; Parotitis; Viruses
PubMed: 20341563
DOI: 10.1016/s0140-6736(47)92295-2 -
Enfermedades Infecciosas Y... Dec 2021This study describes a mumps outbreak among a group of young people who shared a same narghile to smoking. Saliva and blood samples were obtained from 3 cases for RT-PCR...
INTRODUCTION
This study describes a mumps outbreak among a group of young people who shared a same narghile to smoking. Saliva and blood samples were obtained from 3 cases for RT-PCR and serology respectively.
METHODS
The notification of a mumps case started an epidemiological investigation. Information of other 6 additional symptomatic persons who had gathered with the case in a discotheque where they smoking in a same narghile was achieved. RT-PCR positive samples were genotyped by sequencing.
RESULTS
The 7 patients resided in 3 different municipalities, and they do not have get together for more than a month until the meeting in the discotheque. Four cases were confirmed by RT-PCR and/or IgM determinations. The genomic investigation showed identical nucleic sequences.
CONCLUSIONS
This outbreak is consequence of the common use of a narghile to smoking. The public usage of these water pipes should be regulated.
Topics: Adolescent; Disease Outbreaks; Humans; Mumps virus; Smoking; Smoking Water Pipes; Water Pipe Smoking
PubMed: 34531159
DOI: 10.1016/j.eimce.2021.09.002 -
Viruses Dec 2021Frequent mumps outbreaks in vaccinated populations and the occurrence of neurological complications (e.g., aseptic meningitis or encephalitis) in patients with mumps...
Frequent mumps outbreaks in vaccinated populations and the occurrence of neurological complications (e.g., aseptic meningitis or encephalitis) in patients with mumps indicate the need for the development of more efficient vaccines as well as specific antiviral therapies. RNA viruses are genetically highly heterogeneous populations that exist on the edge of an error threshold, such that additional increases in mutational burden can lead to extinction of the virus population. Deliberate modulation of their natural mutation rate is being exploited as an antiviral strategy and a possibility for rational vaccine design. The aim of this study was to examine the ability of ribavirin, a broad-spectrum antiviral agent, to introduce mutations in the mumps virus (MuV) genome and to investigate if resistance develops during long-term in vitro exposure to ribavirin. An increase in MuV population heterogeneity in the presence of ribavirin has been observed after one passage in cell culture, as well as a bias toward C-to-U and G-to-A transitions, which have previously been defined as ribavirin-related. At higher ribavirin concentration, MuV loses its infectivity during serial passaging and does not recover. At low ribavirin concentration, serial passaging leads to a more significant increase in population diversity and a stronger bias towards ribavirin-related transitions, independently of viral strain or cell culture. In these conditions, the virus retains its initial growth capacity, without development of resistance at a whole-virus population level.
Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Drug Resistance, Viral; Genetic Variation; Mumps virus; Mutation; Ribavirin; Vero Cells; Virus Replication
PubMed: 34960805
DOI: 10.3390/v13122535 -
Reviews in Medical Virology Mar 2015The WHO recently proposed an updated nomenclature for mumps virus (MuV). WHO currently recognizes 12 genotypes of MuV, assigned letters from A to N (excluding E and M),... (Review)
Review
The WHO recently proposed an updated nomenclature for mumps virus (MuV). WHO currently recognizes 12 genotypes of MuV, assigned letters from A to N (excluding E and M), which are based on the nucleotide sequences of small hydrophobic (SH) and haemagglutinin-neuraminidase (HN) genes. A total of 66 MuV genomes are available in GenBank, representing eight of the 12 genotypes. To complete this dataset, whole genomes of seven isolates representing six genotypes (D, H, I, J, K and L) and one unclassified strain were sequenced. SH and HN genes of other representative strains were also sequenced. The degree of genetic divergence, predicted amino acid substitutions in the HN and fusion (F) proteins and geographic distributions of MuV strains were analysed based on the updated dataset. Nucleotide heterogeneity between genotypes reached 20% within the SH gene, with a maximum of 9% within the HN gene. The geographic and chronologic distributions of the 12 genotypes were summarised. This review contributes to our understanding of strain diversity for wild type MuV, and the results support the current WHO nomenclature.
Topics: Cluster Analysis; Genetic Variation; Genome, Viral; Genotype; Global Health; HN Protein; Humans; Molecular Sequence Data; Mumps; Mumps virus; Phylogeography; RNA, Viral; Sequence Analysis, DNA; Sequence Homology; Spatio-Temporal Analysis; Viral Proteins
PubMed: 25424978
DOI: 10.1002/rmv.1819 -
Human Vaccines & Immunotherapeutics Dec 2016The recent mumps outbreaks among MMR vaccinated persons have raised questions about the biological mechanisms related to mumps symptoms and complications in the...
The recent mumps outbreaks among MMR vaccinated persons have raised questions about the biological mechanisms related to mumps symptoms and complications in the background of waning immunity. Contrary to other paramyxoviruses, the understanding of mumps virus pathogenesis is limited, and further in-depth clinical studies are required to provide answers to important research questions.
Topics: Child; Child, Preschool; Humans; Knowledge; Mumps; Mumps virus
PubMed: 27455055
DOI: 10.1080/21645515.2016.1210745 -
Virology Journal Jan 2016Mumps virus is a negative-sense, single stranded RNA virus consisting of a ribonucleocapsid core enveloped by a lipid membrane derived from host cell, which causes mumps...
BACKGROUND
Mumps virus is a negative-sense, single stranded RNA virus consisting of a ribonucleocapsid core enveloped by a lipid membrane derived from host cell, which causes mumps disease preventable by vaccination. Since virus lipid envelope and glycosylation pattern are not encoded by the virus but dependent on the host cell at least to some extent, the aim of this work was to analyse L-Zagreb (L-Zg) mumps virus lipids and proteins derived from two cell types; Vero and chicken embryo fibroblasts (CEF). Jeryl Lynn 5 (JL5) mumps strain lipids were also analysed.
METHODS
Virus lipids were isolated by organic phase extraction and subjected to 2D-high performance thin layer chromatography followed by lipid extraction and identification by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Virus samples were also subjected to gel electrophoresis under denaturating conditions and protein bands were excised, in-gel trypsinized and identified by MS as well as tandem MS.
RESULTS
Results showed that lipids of both mumps virus strains derived from Vero cells contained complex glycolipids with up to five monosaccharide units whereas the lipid pattern of mumps virus derived from CEF was less complex. Mumps virus was found to contain expected structural proteins with exception of fusion (F) protein which was not detected but on the other hand, V protein was detected. Most interesting finding related to the mumps proteins is the detection of several forms of nucleoprotein (NP), some of which appear to be C-terminally truncated.
CONCLUSIONS
Differences found in lipid and protein content of mumps virus demonstrated the importance of detailed biochemical characterization of mumps virus and the methodology described here could provide a means for a more comprehensive quality control in vaccine production.
Topics: Amino Acid Sequence; Animals; Chick Embryo; Chlorocebus aethiops; Fibroblasts; Lipids; Mass Spectrometry; Molecular Sequence Data; Mumps virus; Sequence Alignment; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Vero Cells; Viral Proteins
PubMed: 26768080
DOI: 10.1186/s12985-016-0463-0 -
Infection, Genetics and Evolution :... Sep 2004The molecular epidemiology of MuV is characterized by the co-existence of 10 (or more) distinct genotypes named A-J based on the nucleotide sequence of the SH gene. MuV... (Review)
Review
The molecular epidemiology of MuV is characterized by the co-existence of 10 (or more) distinct genotypes named A-J based on the nucleotide sequence of the SH gene. MuV show distinct geographic clustering. More than one genotype may circulate simultaneously in a geographic region. Limited data suggest redistribution of genotypes to occur over time. The selective forces remain speculative. Currently used vaccine strains belong to different genotypes. Some MuV genotypes (C, D, H, J) and vaccine strains (Urabe Am9) have been associated with enhanced neurovirulence. Also, reduced cross-neutralization capacity has been observed between genotype A and genotypes C and D. At present vaccine failure cannot be attributed to this phenomenon. Strain redistribution may lead to the emergence of new MuV strains with enhanced neurovirulence or reduced cross-neutralization capacity with current vaccine strains. Close monitoring of the genotype distribution of MuV and genotype-specific population immunity is needed in the vaccine era.
Topics: Base Sequence; Genome, Viral; Genotype; Humans; Molecular Epidemiology; Mumps; Mumps Vaccine; Mumps virus; Nervous System; Phylogeny
PubMed: 15450201
DOI: 10.1016/j.meegid.2004.02.003