-
Journal of Virology Jul 2013The phosphoprotein (P) is virally encoded by the Rhabdoviridae and Paramyxoviridae in the order Mononegavirales. P is a self-associated oligomer and forms complexes with...
The phosphoprotein (P) is virally encoded by the Rhabdoviridae and Paramyxoviridae in the order Mononegavirales. P is a self-associated oligomer and forms complexes with the large viral polymerase protein (L), the nucleocapsid protein (N), and the assembled nucleocapsid. P from different viruses has shown structural diversities even though their essential functions are the same. We systematically mapped the domains in mumps virus (MuV) P and investigated their interactions with nucleocapsid-like particles (NLPs). Similar to other P proteins, MuV P contains N-terminal, central, and C-terminal domains with flexible linkers between neighboring domains. By pulldown assays, we discovered that in addition to the previously proposed nucleocapsid binding domain (residues 343 to 391), the N-terminal region of MuV P (residues 1 to 194) could also bind NLPs. Further analysis of binding kinetics was conducted using surface plasmon resonance. This is the first observation that both the N- and C-terminal regions of a negative-strand RNA virus P are involved in binding the nucleocapsid. In addition, we defined the oligomerization domain (POD) of MuV P as residues 213 to 277 and determined its crystal structure. The tetrameric MuV POD is formed by one pair of long parallel α-helices with another pair in opposite orientation. Unlike the parallel orientation of each α-helix in the tetramer of Sendai virus POD, this represents a novel orientation of a POD where both the N- and the C-terminal domains are at either end of the tetramer. This is consistent with the observation that both the N- and the C-terminal domains are involved in binding the nucleocapsid.
Topics: Computational Biology; Crystallization; Escherichia coli; Kinetics; Models, Molecular; Mumps virus; Nucleocapsid Proteins; Phosphoproteins; Plasmids; Protein Conformation; Protein Structure, Tertiary; Surface Plasmon Resonance; X-Ray Diffraction
PubMed: 23637399
DOI: 10.1128/JVI.00653-13 -
Journal of Virology Dec 2015Mumps virus (MuV) is an airborne virus that causes a systemic infection in patients. In vivo, the epithelium is a major replication site of MuV, and thus, the mode of...
UNLABELLED
Mumps virus (MuV) is an airborne virus that causes a systemic infection in patients. In vivo, the epithelium is a major replication site of MuV, and thus, the mode of MuV infection of epithelial cells is a subject of interest. Our data in the present study showed that MuV entered polarized epithelial cells via both the apical and basolateral surfaces, while progeny viruses were predominantly released from the apical surface. In polarized cells, intracellular transport of viral ribonucleoprotein (vRNP) complexes was dependent on Rab11-positive endosomes, and vRNP complexes were transported to the apical membrane. Expression of a dominant negative form of Rab11 (Rab11S25N) reduced the progeny virus release in polarized cells but not in nonpolarized cells. Although in this way these effects were correlated with cell polarity, Rab11S25N did not modulate the direction of virus release from the apical surface. Therefore, our data suggested that Rab11 is not a regulator of selective apical release of MuV, although it acts as an activator of virus release from polarized epithelial cells. In addition, our data and previous studies on Sendai virus, respiratory syncytial virus, and measles virus suggested that selective apical release from epithelial cells is used by many paramyxoviruses, even though they cause either a systemic infection or a local respiratory infection.
IMPORTANCE
Mumps virus (MuV) is the etiological agent of mumps and causes a systemic infection. However, the precise mechanism by which MuV breaks through the epithelial barriers and achieves a systemic infection remains unclear. In the present study, we show that the entry of MuV is bipolar, while the release is predominantly from the apical surface in polarized epithelial cells. In addition, the release of progeny virus was facilitated by a Rab11-positive recycling endosome and microtubule network. Our data provide important insights into the mechanism of transmission and pathogenesis of MuV.
Topics: Animals; Chlorocebus aethiops; Dogs; Endosomes; Epithelial Cells; Green Fluorescent Proteins; Humans; Immunoblotting; Microscopy, Fluorescence; Mumps virus; Plasmids; Virus Release; rab GTP-Binding Proteins
PubMed: 26378159
DOI: 10.1128/JVI.02048-15 -
The Journal of Infectious Diseases Jan 2017To evaluate the antigenic relationship between bat mumps virus (BMV) and the JL5 vaccine strain of mumps virus (MuVJL5), we rescued a chimeric virus bearing the F and HN...
To evaluate the antigenic relationship between bat mumps virus (BMV) and the JL5 vaccine strain of mumps virus (MuVJL5), we rescued a chimeric virus bearing the F and HN glycoproteins of BMV in the background of a recombinant JL5 genome (rMuVJL5). Cross-reactivity and cross-neutralization between this chimeric recombinant MuV bearing the F and HN glycoproteins of BMV (rMuVJL5-F/HNBMV) virus and rMuVJL5 were demonstrated using hyperimmune mouse serum samples and a curated panel of human serum. All mouse and human serum samples that were able to neutralize rMuVJL5 infection had cross-neutralizing activity against rMuVJL5-F/HNBMV. Our data suggest that persons who have neutralizing antibodies against MuV might be protected from infection by BMV.
Topics: Adolescent; Adult; Animals; Antibodies, Neutralizing; Antibodies, Viral; Chiroptera; Cross Reactions; Female; Humans; Mice, Inbred BALB C; Middle Aged; Mumps virus; Young Adult
PubMed: 27811320
DOI: 10.1093/infdis/jiw534 -
Journal of Neurology Oct 2021A positive MRZ reaction, as defined by intrathecal IgG production against at least two of its constituents, measles virus (M), rubella virus (R) and varicella zoster...
Parvovirus B19 and mumps virus antibodies are major constituents of the intrathecal immune response in European patients with MS and increase the diagnostic sensitivity and discriminatory power of the MRZ reaction.
BACKGROUND
A positive MRZ reaction, as defined by intrathecal IgG production against at least two of its constituents, measles virus (M), rubella virus (R) and varicella zoster virus (Z), is detectable in ~ 63% of patients with multiple sclerosis (MS) and is currently considered the laboratory marker with the highest specificity and positive likelihood ratio for MS. However, M, R and Z are only the most well-established constituents of a broader intrathecal humoral immune response in MS.
OBJECTIVE
To identify additional anti-microbial antibodies inclusion of which in the classical MRZ panel may result in increased sensitivity without compromising the marker's high specificity for MS.
METHODS
We determined the antibody indices (AIs) for 11 viral and bacterial agents (M, R, Z, herpes simplex virus, Epstein-Barr virus, mumps virus, cytomegalovirus, parvovirus B19, Bordetella pertussis, Corynebacterium diphtheriae, and Clostridium tetani) in paired cerebrospinal fluid and serum samples from patients with MS and disease controls.
RESULTS
A positive 'classical' MRZ reaction was found in 17/26 (65.4%) MS patients. The five most frequently positive AIs among patients with MS were M (76.9%), Z (61.5%), R (57.7%), parvovirus B19 (42.3%), and mumps (28%). Addition of parvovirus B19 and mumps virus to the MRZ panel resulted in an increase in sensitivity in the MS group from 65.4% to 73.1%, with 22% of the initially MRZ-negative patients exhibiting a de novo-positive response. The extended MRZ panel ('MRZplus') distinguished sharply between MS (≥ 3 AIs in 90% of all positives) and controls (varying diagnoses, from migraine to vasculitis; 0-1 AIs; p < 0.000001). The highest median AI in the MS group was found for parvovirus B19 (3.97), followed by measles virus (2.79).
CONCLUSION
Inclusion of parvovirus B19 and mumps virus in the test panel resulted in an increase in the sensitivity and discriminatory power of MRZ. Our results provide a strong rational for prospective studies investigating the role of extended MRZ panels in the differential diagnosis of MS.
Topics: Antibodies, Viral; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Immunity; Multiple Sclerosis; Mumps virus; Parvovirus B19, Human; Prospective Studies
PubMed: 33770235
DOI: 10.1007/s00415-021-10471-3 -
PloS One 2015Mumps viruses show diverse cytopathic effects (CPEs) of infected cells and viral plaque formation (no CPE or no plaque formation in some cases) depending on the viral...
Mumps viruses show diverse cytopathic effects (CPEs) of infected cells and viral plaque formation (no CPE or no plaque formation in some cases) depending on the viral strain, highlighting the difficulty in mumps laboratory studies. In our previous study, a new sialidase substrate, 2-(benzothiazol-2-yl)-4-bromophenyl 5-acetamido-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosidonic acid (BTP3-Neu5Ac), was developed for visualization of sialidase activity. BTP3-Neu5Ac can easily and rapidly perform histochemical fluorescent visualization of influenza viruses and virus-infected cells without an antiviral antibody and cell fixation. In the present study, the potential utility of BTP3-Neu5Ac for rapid detection of mumps virus was demonstrated. BTP3-Neu5Ac could visualize dot-blotted mumps virus, virus-infected cells, and plaques (plaques should be called focuses due to staining of infected cells in this study), even if a CPE was not observed. Furthermore, virus cultivation was possible by direct pick-up from a fluorescent focus. In conventional methods, visible appearance of the CPE and focuses often requires more than 6 days after infection, but the new method with BTP3-Neu5Ac clearly visualized infected cells after 2 days and focuses after 4 days. The BTP3-Neu5Ac assay is a precise, easy, and rapid assay for confirmation and titration of mumps virus.
Topics: Animals; Chlorocebus aethiops; Fluorescence; Humans; Mumps virus; Vero Cells
PubMed: 26629699
DOI: 10.1371/journal.pone.0144038 -
Journal of Virology Jul 2011Mumps virus (MuV) is highly neurotropic and was the leading cause of aseptic meningitis in the Western Hemisphere prior to widespread use of live attenuated MuV...
Mumps virus (MuV) is highly neurotropic and was the leading cause of aseptic meningitis in the Western Hemisphere prior to widespread use of live attenuated MuV vaccines. Due to the absence of markers of virus neuroattenuation and neurovirulence, ensuring mumps vaccine safety has proven problematic, as demonstrated by the occurrence of aseptic meningitis in recipients of certain vaccine strains. Here we examined the genetic basis of MuV neuroattenuation and neurovirulence by generating a series of recombinant viruses consisting of combinations of genes derived from a cDNA clone of the neurovirulent wild-type 88-1961 strain (r88) and from a cDNA clone of the highly attenuated Jeryl Lynn vaccine strain (rJL). Testing of these viruses in rats demonstrated the ability of several individual rJL genes and gene combinations to significantly neuroattenuate r88, with the greatest effect imparted by the rJL nucleoprotein/matrix protein combination. Interestingly, no tested combination of r88 genes, including the nucleoprotein/matrix protein combination, was able to convert rJL into a highly neurovirulent virus, highlighting mechanistic differences between processes involved in neuroattenuation and neurovirulence.
Topics: Animals; Attention; Central Nervous System; Chlorocebus aethiops; Genes, Viral; Mumps virus; Rats; Rats, Inbred Lew; Reverse Transcriptase Polymerase Chain Reaction; Vero Cells; Virulence; Virus Replication
PubMed: 21543475
DOI: 10.1128/JVI.00245-11 -
Medicine Sep 2021Mumps is an acute and common childhood disease caused by paramyxovirus. It has been reported that the occurrence of mumps is influenced by seasonality. However, the role... (Observational Study)
Observational Study
Mumps is an acute and common childhood disease caused by paramyxovirus. It has been reported that the occurrence of mumps is influenced by seasonality. However, the role of meteorological variables in the incidence of mumps remains unclear. The purpose of this study was to explore the relationship between meteorological factors and the incidence of mumps infection. Poisson regression analysis was used to study the relationship between weather variability and the incidence of mumps in Taiwan. Between 2012 and 2018, 5459 cases of mumps cases were reported to the Centers for Disease Control, Taiwan (Taiwan CDC). The occurrence of mumps virus infections revealed significant seasonality in the spring and summer seasons in Taiwan. The incidence of mumps virus infections began to increase at temperatures of 15°C and started to decline if the temperature was higher than 29°C (r2 = 0.387, P = .008). Similarly, the number of mumps cases began to increase at a relative humidity of 65% to 69% (r2 = 0.838, P < .029). The number of mumps cases was positively associated with temperature and relative humidity during the period preceding the infection. This study showed that the occurrence of mumps is significantly associated with increasing temperature and relative humidity in Taiwan. Therefore, these factors could be regarded as early warning signals and indicate the need to strengthen the intervention and prevention of mumps.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Incidence; Male; Meteorological Concepts; Mumps; Regression Analysis; Seasons; Taiwan
PubMed: 34664880
DOI: 10.1097/MD.0000000000027267 -
Cell Reports Oct 2018Bats harbor a plethora of viruses with an unknown zoonotic potential. In-depth functional characterization of such viruses is often hampered by a lack of...
Bats harbor a plethora of viruses with an unknown zoonotic potential. In-depth functional characterization of such viruses is often hampered by a lack of virus isolates. The genome of a virus closely related to human mumps viruses (hMuV) was detected in African fruit bats, batMuV. Efforts to characterize batMuV were based on directed expression of the batMuV glycoproteins or use of recombinant chimeric hMuVs harboring batMuV glycoprotein. Although these studies provided initial insights into the functionality of batMuV glycoproteins, the host range, replication competence, immunomodulatory functions, virulence, and zoonotic potential of batMuV remained elusive. Here, we report the successful rescue of recombinant batMuV. BatMuV infects human cells, is largely resistant to the host interferon response, blocks interferon induction and TNF-α activation, and is neurotoxic in rats. Anti-hMuV antibodies efficiently neutralize batMuV. The striking similarities between hMuV and batMuV point at the putative zoonotic potential of batMuV.
Topics: Animals; Chiroptera; Female; Humans; Immune Evasion; Mumps; Mumps virus; Neurotoxicity Syndromes; Rats; Rats, Inbred Lew; Virus Internalization; Virus Replication
PubMed: 30304672
DOI: 10.1016/j.celrep.2018.09.018 -
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 -
The Journal of Infectious Diseases Sep 2019The plaque reduction neutralization test (PRNT), which measures a subset of immunoglobulin antibodies (functional neutralizing antibodies), and the enzyme-linked... (Comparative Study)
Comparative Study
BACKGROUND
The plaque reduction neutralization test (PRNT), which measures a subset of immunoglobulin antibodies (functional neutralizing antibodies), and the enzyme-linked immunosorbent assay (ELISA), which measures total immunoglobulin (neutralizing and nonneutralizing antibodies), characterize different aspects of the anti-mumps virus antibody response after vaccination.
METHODS
Data from a recent phase 3 clinical trial (NCT01681992) of 2 measles-mumps-rubella vaccines were used to compare anti-mumps antibody responses measured using an unenhanced PRNT (GSK; seropositivity cutoff and threshold, 2.5 and 4 times the 50% end-point dilution, respectively) with those estimated using an ELISA (thresholds, 5 and 10 ELISA units/mL, respectively).
RESULTS
Of 3990 initially seronegative samples, 3284 (82.3%) were seropositive after vaccination for anti-mumps antibodies in both assays. The Pearson correlation coefficient for double-positive samples was 0.57, indicative of a moderate correlation. Receiver operating characteristic curve analysis showed that an ELISA threshold of 51.7 ELISA units/mL best corresponded to the PRNT seroresponse threshold. There was no obvious vaccine brand effect on the correlation between assays.
CONCLUSIONS
The moderate correlation between the anti-mumps antibody measurements obtained with PRNT and ELISA reflects different aspects of the serological response. In the absence of a well-defined protective serological threshold, PRNT provides complementary information on the antibody response, whereas ELISA remains a critically useful measurement of vaccine immunogenicity.
Topics: Antibodies, Neutralizing; Antibodies, Viral; Clinical Trials, Phase III as Topic; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Male; Measles-Mumps-Rubella Vaccine; Mumps virus; Neutralization Tests; ROC Curve; Viral Plaque Assay
PubMed: 31299077
DOI: 10.1093/infdis/jiz345