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Virology Journal Jun 2018In September 2009, a mumps outbreak originated in New York and spread to Northeastern USA and Canada. This study compares the performance of different diagnostic testing...
BACKGROUND
In September 2009, a mumps outbreak originated in New York and spread to Northeastern USA and Canada. This study compares the performance of different diagnostic testing methods used in Ontario and describes molecular characteristics of the outbreak strain.
METHODS
Between September 2009 and February 2010, specimens from suspect cases were submitted to Public Health Ontario Laboratory for mumps serology, culture and/or real-time reverse-transcriptase PCR (rRT-PCR) testing. rRT-PCR-positive specimens underwent genotyping at Canada's National Microbiology Laboratory. Whole genome sequencing was performed on four outbreak and three sporadic viral culture isolates.
RESULTS
Six hundred ninety-eight patients had IgM serology testing, of which 255 (37%) had culture and rRT-PCR. Among those, 35/698 (5%) were IgM positive, 39/255 (15%) culture positive and 47/255 (18%) rRT-PCR-positive. Buccal swabs had the highest rRT-PCR positivity (21%). The outbreak isolates were identical to that in the New York outbreak occurring at the same time. Nucleotide and amino acid identity with the Jeryl Lynn vaccine strain ranged from 85.0-94.5% and 82.4-99.4%, depending on the gene and coding sequences. Homology of the HN protein, the main immunogenic mumps virus protein, was found to be 94.5 and 95.3%, when compared to Jeryl Lynn vaccine major and minor components, respectively.
CONCLUSIONS
Despite higher sensitivity than serology, rRT-PCR testing is underutilized. Further work is needed to better understand the suboptimal match of the HN gene between the outbreak strain and the Jeryl Lynn vaccine strain.
Topics: Clinical Laboratory Techniques; Disease Outbreaks; HN Protein; Humans; Immunoglobulin M; Mumps; Mumps virus; New York; Ontario; Phylogeny; RNA, Viral; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid
PubMed: 29866178
DOI: 10.1186/s12985-018-0996-5 -
ELife Apr 2021In 2016/2017, Washington State experienced a mumps outbreak despite high childhood vaccination rates, with cases more frequently detected among school-aged children and...
In 2016/2017, Washington State experienced a mumps outbreak despite high childhood vaccination rates, with cases more frequently detected among school-aged children and members of the Marshallese community. We sequenced 166 mumps virus genomes collected in Washington and other US states, and traced mumps introductions and transmission within Washington. We uncover that mumps was introduced into Washington approximately 13 times, primarily from Arkansas, sparking multiple co-circulating transmission chains. Although age and vaccination status may have impacted transmission, our data set could not quantify their precise effects. Instead, the outbreak in Washington was overwhelmingly sustained by transmission within the Marshallese community. Our findings underscore the utility of genomic data to clarify epidemiologic factors driving transmission and pinpoint contact networks as critical for mumps transmission. These results imply that contact structures and historic disparities may leave populations at increased risk for respiratory virus disease even when a vaccine is effective and widely used.
Topics: Adolescent; Adult; Child; Child, Preschool; Disease Outbreaks; Genome, Viral; Humans; Infant; Micronesia; Middle Aged; Mumps; Mumps virus; Washington; Young Adult
PubMed: 33871357
DOI: 10.7554/eLife.66448 -
Microbiology Spectrum Oct 2021Bats are a reservoir for many zoonotic viruses and host large numbers of genetically diverse species in the families , , and . Viruses from these families have...
Bats are a reservoir for many zoonotic viruses and host large numbers of genetically diverse species in the families , , and . Viruses from these families have repeatedly spilled over to humans in recent decades, causing significant clinical disease and deaths. Here, metagenomic sequencing of a big brown bat (Eptesicus fuscus) submitted for rabies testing due to human exposure identified a novel paramyxovirus, Eptesicus fuscus orthorubulavirus (EfORV), in South Dakota, United States. The nearly complete 15,814-nucleotide genome shared 72% identity with that of human parainfluenza virus 4 (HPIV4), a virus that causes significant clinical disease, typically bronchiolitis and pneumonia, in children less than 2 years of age. Phylogenetic analysis confirmed a close evolutionary history between EfORV and HPIV4, reminiscent of other orthorubulaviruses with highly similar bat and mammalian species, including conspecific human and bat mumps virus, mammalian parainfluenza virus 5 and bat Alston virus, and porcine La Piedad Michoacán virus and bat Mapuera virus. These results support the idea that bats are a reservoir for diverse paramyxoviruses with closely shared evolutionary histories, compared with a number of significant human pathogens, and expand the range of bat paramyxoviruses to North America. Given the propensity of paramyxoviruses to overcome species barriers, additional surveillance and characterization of EfORV are warranted. Bats are a reservoir of large numbers of viruses. Among bat-borne zoonotic viruses, members of and have had the largest impact on human health. The repeated spillover of bat viruses to humans, often with devastating results, has led to increased surveillance and virus discovery efforts in hot spots for virus emergence, largely Asia and Africa. Apart from rabies virus, little surveillance of viruses in bats is performed in North America. Here, viral metagenomic sequencing identified a close relative to HPIV4 in a big brown bat found in a motel room in South Dakota. The virus, EfORV, was 72% identical to HPIV4, which causes clinically significant respiratory disease, mainly in children; it represents the first bat paramyxovirus identified in North America. Close genetic relationships between bat and mammalian orthorubulaviruses underscore the importance of bats as a reservoir for zoonotic viruses.
Topics: Animals; Chiroptera; Disease Reservoirs; Genome, Viral; Humans; Metagenomics; Parainfluenza Virus 4, Human; Paramyxoviridae; South Dakota; Zoonoses
PubMed: 34668744
DOI: 10.1128/Spectrum.00930-21 -
Uirusu 2021Mumps virus (MuV) is the causative agent of mumps, a common childhood illness characterized by fever and swelling of the salivary glands. Like other viral infections, a...
Mumps virus (MuV) is the causative agent of mumps, a common childhood illness characterized by fever and swelling of the salivary glands. Like other viral infections, a number of host proteins are thought to involve in MuV infection. We have shown the function of several host factors in MuV infection. The chaperone proteins, heat shock protein 70 (Hsp70) and Hsp90, interact with the P and L proteins that form the polymerase complex and function in the protein quality control of these viral proteins, and thus they are essential host factors in MuV RNA synthesis. The R2TP complex is a host factor that contributes to effective viral propagation by precise regulation of viral RNA synthesis and evasion of host immune responses, and Rab11 is a host factor involved in viral RNP trafficking to the plasma membrane. This article summarizes the functions of host factors involved in MuV infection based on our researches.
Topics: HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Host-Pathogen Interactions; Humans; Mumps; Mumps virus; RNA, Viral; Viral Proteins
PubMed: 35526997
DOI: 10.2222/jsv.71.71 -
Viruses Dec 2021Recombinant mumps viruses (MuVs) based on established vaccine strains represent attractive vector candidates as they have known track records for high efficacy and the...
Recombinant mumps viruses (MuVs) based on established vaccine strains represent attractive vector candidates as they have known track records for high efficacy and the viral genome does not integrate in the host cells. We developed a rescue system based on the consensus sequence of the L-Zagreb vaccine and generated seven different recombinant MuVs by (a) insertion of one or two additional transcription units (ATUs), (b) lengthening of a noncoding region to the extent that the longest noncoding region in MuV genome is created, or (c) replacement of original L-Zagreb sequences with sequences rich in CG and AT dinucleotides. All viruses were successfully rescued and faithfully matched sequences of input plasmids. In primary rescued stocks, low percentages of heterogeneous positions were found (maximum 0.12%) and substitutions were predominantly obtained in minor variants, with maximally four substitutions seen in consensus. ATUs did not accumulate more mutations than the natural MuV genes. Six substitutions characteristic for recombinant viruses generated in our system were defined, as they repetitively occurred during rescue processes. In subsequent passaging of primary rescue stocks in Vero cells, different inconsistencies within quasispecies structures were observed. In order to assure that unwanted mutations did not emerge and accumulate, sub-consensus variability should be closely monitored. As we show for Pro408Leu mutation in L gene and a stop codon in one of ATUs, positively selected variants can rise to frequencies over 85% in only few passages.
Topics: Animals; Chlorocebus aethiops; Genome, Viral; Mumps virus; Mutation; Plasmids; Recombination, Genetic; Vero Cells
PubMed: 34960819
DOI: 10.3390/v13122550 -
Canadian Medical Association Journal Feb 1964Between January and June 1963, 45 children were hospitalized with mumps meningoencephalitis. Of 39 patients with laboratory evidence of mumps infection, 24 had parotitis...
Between January and June 1963, 45 children were hospitalized with mumps meningoencephalitis. Of 39 patients with laboratory evidence of mumps infection, 24 had parotitis and 15 showed no salivary gland involvement. Cerebrospinal fluids from 18 of 40 patients yielded mumps virus by inoculation of rhesus monkey kidney cultures; 33 subjects, including 12 of the 18 virus excretors, showed rising or elevated levels of mumps antihemagglutinin during convalescence. Between May 1959 and June 1963, mumps virus was recovered from cerebrospinal fluids of 50 of 126 cases of mumps meningoencephalitis; virus isolation rates were highest during the peak incidence of mumps meningoencephalitis in winter and early spring.Mumps vaccine (inactivated) was administered to 34 parents with no history of mumps, shortly after their children developed mumps. Mumps occurred in three of 17 parents without prevaccination mumps antihemagglutinins, and in two others, but in none of 15 who had prevaccination antibodies.
Topics: Antibodies; Antigen-Antibody Reactions; Canada; Child; Child, Preschool; Encephalitis, Viral; Epidemiology; Humans; Meningitis, Viral; Meningoencephalitis; Mumps; Mumps Vaccine; Mumps virus; Seasons; Vaccination; Vaccines
PubMed: 14120950
DOI: No ID Found -
Journal of Virology Feb 2015In the extracellular environment, cell-free virions seek out naive host cells over long distances and between organisms. This is the primary mechanism of spread for most...
UNLABELLED
In the extracellular environment, cell-free virions seek out naive host cells over long distances and between organisms. This is the primary mechanism of spread for most viruses. Here we provide evidence for an alternative pathway previously undescribed for orthomyxoviruses, whereby the spread of influenza A virus (IAV) infectious cores to neighboring cells can occur within intercellular connections. The formation of these connections requires actin dynamics and is enhanced by viral infection. Connected cells have contiguous membranes, and the core infectious viral machinery (RNP and polymerase) was present inside the intercellular connections. A live-cell movie of green fluorescent protein (GFP)-tagged NS1 of IAV shows viral protein moving from one cell to another through an intercellular connection. The movement of tagged protein was saltatory but overall traveled only in one direction. Infectious virus cores can move from one cell to another without budding and release of cell-free virions, as evidenced by the finding that whereas a neuraminidase inhibitor alone did not inhibit the development of IAV microplaques, the presence of a neuraminidase inhibitor together with drugs inhibiting actin dynamics or the microtubule stabilizer paclitaxel (originally named taxol) precluded microplaque formation. Similar results were also observed with parainfluenza virus 5 (PIV5), a paramyxovirus, when neutralizing antibody was used to block spread by cell-free virions. Intercellular spread of infectious core particles was unaffected or enhanced in the presence of nocodazole for IAV but inhibited for PIV5. The intercellular connections have a core of filamentous actin, which hints toward transport of virus particles through the use of a myosin motor.
IMPORTANCE
Here we describe a new method by which influenza A virus (IAV) spreads from cell to cell: IAV uses intracellular connections. The formation of these connections requires actin dynamics and is enhanced by viral infection and the absence of microtubules. Connected cells appeared to have contiguous membranes, and the core infectious viral machinery (RNP and polymerase) was present inside the intercellular connections. Infectious virus cores can move from one cell to another without budding and release of cell-free virions. Similar results were also observed with parainfluenza virus 5 (PIV5).
Topics: Actins; Animals; Cell Line; Humans; Influenza A virus; Intercellular Junctions; Microscopy, Fluorescence; Microscopy, Video; Parainfluenza Virus 5; Virus Internalization
PubMed: 25428869
DOI: 10.1128/JVI.03306-14 -
Viruses Jan 2019The Egyptian rousette bat () has previously been implicated as the natural host of a zoonotic rubulavirus; however, its association with rubulaviruses has been studied...
The Egyptian rousette bat () has previously been implicated as the natural host of a zoonotic rubulavirus; however, its association with rubulaviruses has been studied to a limited extent. Urine, spleen, and other organs collected from the population within South Africa were tested with a hemi-nested RT-PCR assay targeting a partial polymerase gene region of viruses from the - and genera. Urine was collected over a 14-month period to study the temporal dynamics of viral excretion. Diverse rubulaviruses, including viruses related to human mumps and parainfluenza virus 2, were detected. Active excretion was identified during two peak periods coinciding with the host reproductive cycle. Analysis of additional organs indicated co-infection of individual bats with a number of different putative rubulaviruses, highlighting the limitations of using a single sample type when determining viral presence and diversity. Our findings suggest that can harbor a range of - and related viruses, some of which are related to known human pathogens. The observed peaks in viral excretion represents potential periods of a higher risk of virus transmission and zoonotic disease spill-over.
Topics: Animals; Avulavirus; Avulavirus Infections; Chiroptera; Disease Reservoirs; Egypt; Longitudinal Studies; Phylogeny; Polymerase Chain Reaction; RNA, Viral; Rubulavirus; Rubulavirus Infections; South Africa; Spleen; Urine
PubMed: 30626055
DOI: 10.3390/v11010037 -
Journal of Virology Jul 2009Mumps virus, like other paramyxoviruses in the Rubulavirus genus, encodes a V protein that can assemble a ubiquitin ligase complex from cellular components, leading to...
Mumps virus, like other paramyxoviruses in the Rubulavirus genus, encodes a V protein that can assemble a ubiquitin ligase complex from cellular components, leading to the destruction of cellular signal transducer and activator of transcription (STAT) proteins. While many V proteins target the interferon-activated STAT1 or STAT2 protein, mumps virus V protein is unique in its ability to also target STAT3 for ubiquitin modification and proteasome-mediated degradation. Here we report that a single amino acid substitution in the mumps virus V protein, E95D, results in defective STAT3 targeting while maintaining the ability to target STAT1. Results indicate that the E95D mutation disrupts the ability of the V protein to associate with STAT3. A recombinant mumps virus carrying the E95D mutation in its P and V proteins replicates normally in cultured cells but fails to induce targeting of STAT3. Infection with the recombinant virus results in the differential regulation of a number of cellular genes compared to wild-type mumps virus and increases cell death in infected cells, producing a large-plaque phenotype.
Topics: Amino Acid Substitution; Animals; Chlorocebus aethiops; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Mice; Mumps; Mumps virus; Mutagenesis, Site-Directed; Oligonucleotide Array Sequence Analysis; Point Mutation; STAT1 Transcription Factor; STAT3 Transcription Factor; Vero Cells; Viral Proteins
PubMed: 19386700
DOI: 10.1128/JVI.00596-09 -
Virology Journal Dec 2022Since the onset of the coronavirus disease-2019 (COVID-19) pandemic, the prevalence of respiratory infectious diseases, particularly, the flu epidemic, has considerably...
BACKGROUND
Since the onset of the coronavirus disease-2019 (COVID-19) pandemic, the prevalence of respiratory infectious diseases, particularly, the flu epidemic, has considerably decreased. The low detection rate and decreased number of specimens have hindered the implementation of the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS), a sentinel surveillance system. Most patients with influenza-like illness visit the COVID-19 screening clinic; therefore, the number of samples collected in sentinel surveillance has decreased by more than 50%. Thus, the Korea Disease Control and Prevention Agency supplemented sentinel surveillance with non-sentinel surveillance by private medical diagnostic centers. We report here a delayed and unprecedented high detection of human parainfluenza virus (hPIV) in the Republic of Korea during the COVID-19 pandemic through sentinel and non-sentinel surveillance. We also examined the causes and implications of the changes in prevalence of hPIV.l METHODS: We collected data for 56,984 and 257,217 samples obtained through sentinel and non-sentinel surveillance, respectively. Eight viruses were confirmed using real-time reverse transcription-polymerase chain reaction (PCR) or real-time PCR. Some specimens from the sentinel surveillance were used for genetic characterization of hPIV type 3.
RESULTS
In 2020, hPIV was rarely detected; however, it was detected in August 2021. The detection rate continued to increase considerably in September and reached over 70% in October, 2021. The detection rate of hPIV3 was significantly higher in infants and preschoolers aged 0-6 years in both sentinel and non-sentinel surveillance. Detection of hPIV was delayed in metropolitan areas compared to that in suburban regions. The hemagglutinin-neuraminidase sequences of hPIV3 generated in 2021 were not distinct from those detected prior to the COVID-19 pandemic.
CONCLUSIONS
The operation of non-sentinel and sentinel surveillance to monitor respiratory viruses could sensitively detect an unprecedented revival of hPIV in the Republic of Korea during the COVID-19 pandemic.
Topics: Infant; Humans; Pandemics; Influenza, Human; COVID-19; Parainfluenza Virus 1, Human; Coronavirus; Parainfluenza Virus 2, Human; Respiratory Tract Infections
PubMed: 36510212
DOI: 10.1186/s12985-022-01938-4