Mumps Virus Infection Research Articles

SLC35A2 modulates paramyxovirus fusion events during infection.

Paramyxoviruses are significant human and animal pathogens that include mumps virus (MuV), Newcastle disease virus (NDV) and the murine parainfluenza virus Sendai (SeV). Despite their importance, few host factors implicated in paramyxovirus infection are known. Using a recombinant SeV expressing destabilized GFP (rSeVCdseGFP) in a loss-of-function CRISPR screen, we identified the CMP-sialic acid transporter (CST) gene SLC35A1 and the UDP-galactose transporter (UGT) gene SLC35A2 as essential for paramyxovirus infection. SLC35A1 knockout (KO) cells showed significantly reduced binding and infection of SeV, NDV and MuV due to the lack of cell surface sialic acids, which act as their receptors. However, SLC35A2 KO cells revealed unknown critical roles for this factor in virus-cell and cell-to-cell fusion events during infection with different paramyxoviruses. While the UGT was essential for virus-cell fusion during SeV entry to the cell, it was not required for NDV or MuV entry. Importantly, the UGT promoted the formation of larger syncytia during MuV infection, suggesting a role in cell-to-cell virus spread. Our findings demonstrate that paramyxoviruses can bind to or enter A549 cells in the absence of canonical galactose-bound sialic-acid decorations and show that the UGT facilitates paramyxovirus fusion processes involved in entry and spread.

Exploration of microRNAs as transcriptional regulator in mumps virus infection through computational studies

Mumps is a common childhood infection caused by the mumps virus (MuV). Aseptic meningitis and encephalitis are usual symptoms of mumps together with orchitis and oophoritis that can arise in males and females, respectively. We have used computational tools: RNA22, miRanda and psRNATarget to predict the microRNA-mRNA binding sites to find the putative microRNAs playing role in the host response to mumps virus infection. Our computational studies indicate that hsa-mir-3155a is most likely involved in mumps infection. This was further investigated by the prediction of binding sites of hsa-mir-3155a to the MuV genome. Additionally, structure prediction using MC-Fold and MC-Sym, respectively has been applied to predict the 3D structures of miRNA and mRNA. The miRNA-mRNA interaction profile between has been confirmed through molecular docking simulation studies. Taken together, the putative miRNA (hsa_miR_6794_5p) has been found to be most likely involved in the regulation of transcriptional activity in the MuV infection.

Novel sialidase inhibitors suppress mumps virus replication and infection.

The prevalent human pathogen, mumps virus (MuV; orthorubulavirus parotitidis) causes various complications and serious sequelae, such as meningitis, encephalitis, deafness, and impaired fertility. Direct-acting antivirals (DAAs) targeting MuV which can prevent mumps and mumps-associated complications and sequelae are yet to be developed. Paramyxoviridae family members, such as MuV, possess viral surface hemagglutinin-neuraminidase (HN) protein with sialidase activity which facilitates efficient viral replication. Therefore, to develop DAAs targeting MuV we synthesized MuV sialidase inhibitors. It is proposed that the viral HN has a single functional site for N-acetylneuraminic acid (Neu5Ac) binding and sialidase activity. Further, the known MuV sialidase inhibitor is an analog of Neu5Ac-2,3-didehydro-2-deoxy-N-acetylneuraminic acid (DANA)-which lacks potency. DANA derivatives with higher MuV sialidase inhibitory potency are lacking. The MuV-HN-Neu5Ac binding site has a hydrophobic cavity adjacent to the C4 position of Neu5Ac. Exploiting this, here, we synthesized DANA derivatives with increasing hydrophobicity at its C4 position and created 3 novel sialidase inhibitors (Compounds 1, 2, and 3) with higher specificity for MuV-HN than DANA; they inhibited MuV replication step to greater extent than DANA. Furthermore, they also inhibited hemagglutination and the MuV infection step. The insight-that these 3 novel DANA derivatives possess linear hydrocarbon groups at the C4-hydroxyl group of DANA-could help develop highly potent sialidase inhibitors with high specificity for MuV sialidase, which may function as direct-acting MuV-specific antivirals.

Cytotoxic and viricidal effects of human semen on mumps virus-infected lymphocytes: In vitro studies.

Viruses in human semen may be sexually transmitted via free and cell-mediated viral infection. The potential effects of semen on the infection and sexual transmission of most viruses in semen remain largely unclear. The present study elucidated the inhibitory effects of human seminal plasma (SP) on Jurkat cell (JC)-mediated mumps virus (MuV) infection. We demonstrated that MuV efficiently infected JCs and that the JCs infected by MuV (JC-MuV) mediated MuV infection of HeLa cells. Remarkably, SP was highly cytotoxic to JCs and inhibited JC-MuV infection of HeLa cells. The cytotoxic factor possessed a molecular weight of less than 3 kDa, whereas that of the viricidal factor was over 100 kDa. The cooperation of cytotoxic and viricidal factors was required for the SP inhibition of JC-MuV infection, and prostatic fluid (PF) was responsible for both the cytotoxic and viricidal effects of SP. The cytotoxic effects we observed were resistant to the treatment of PF with boiling water, proteinase K, RNase A, and DNase I. Our results provide novel insights into the antiviral properties of SP, which may limit cell-mediated sexual viral transmission.

MicroRNAs control the transcriptional profiling in mumps virus infection: A computational analysis

MicroRNAs control the transcriptional profiling in mumps virus infection: A computational analysis

Booster doses of an inactivated F genotype mumps vaccine enhance immunogenicity in mice

The mumps virus (MuV) causes a highly contagious human disease characterized by swelling of the parotid glands. Although the administration of an attenuated Jeryl Lynn (JL) MuV vaccine shows efficacy in reducing the incidence of MuV infection, sporadic mumps outbreaks still occur in vaccinated populations. We have previously established that an inactivated F genotype mumps vaccine has a higher neutralizing antibody titer against diverse circulating mumps viruses in mice. Here, we aimed to develop a vaccination strategy to enhance the immune response for MuV and assess the effects of heterologous vaccination compared with homologous approaches. We administered an inactivated F genotype mumps vaccine booster following a homologous prime-boost regime and compared its efficacy with three doses of homologous JL vaccine in mice. We demonstrated robust stimulation of neutralizing antibodies and cellular immune response of interferon-γ-secreting cytotoxic T cells following administration of an inactivated F genotype mumps vaccine booster after a homologous prime-boost regime with JL. Compared with the homologous prime-boost regime, this heterologous prime-boost regime showed protective efficacy against the F genotype of MuV. These findings suggest that the heterologous vaccination strategy based on the administration of an inactivated F genotype mumps vaccine provides more effective cross-protection against circulating wild-type mumps viruses than homologous vaccination.

Evaluation of the Interactions between Mumps Virus and Guinea Pig

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.

SNARE protein USE1 is involved in the glycosylation and the expression of mumps virus fusion protein and important for viral propagation.

Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. To understand the molecular mechanism of MuV infection, a functional analysis of the involved host factors is required. However, little is known about the host factors involved in MuV infection, especially those involved in the late stage of infection. Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. In addition, USE1 plays a role in complete N-linked glycosylation and expression of the MuV F protein.

Antibody Levels at 3-Years Follow-Up of a Third Dose of Measles-Mumps-Rubella Vaccine in Young Adults.

Mumps outbreaks and breakthrough infections of measles and rubella have raised concerns about waning of vaccine-induced immunity after two doses of measles-mumps-rubella (MMR) vaccination. In the present follow-up study, serum IgG antibodies against mumps, measles and rubella, as well as the functional neutralizing antibodies against both the mumps vaccine strain and mumps outbreak strains were measured longitudinally in young adults that received a third MMR (MMR3) dose. The mumps-specific IgG and virus neutralizing antibody levels at 3 years after vaccination were still elevated compared to pre-vaccination antibody levels, although the differences were smaller than at earlier timepoints. Interestingly, subjects with low antibody levels to mumps before vaccination benefited the most as they showed the strongest antibody increase after an MMR3 dose. Three years after an MMR3 dose, all subjects had antibody levels to measles and rubella above the internationally agreed antibody cutoff levels for clinical protection. Our data support the recommendation that an MMR3 dose may provide additional protection for those that have become susceptible to mumps virus infection during outbreaks. MMR3 also resulted in an increase in anti-measles and rubella antibody levels that lasted longer than might have been expected.

Incidence of Mumps Deafness in Japan, 2005-2017: Analysis of Japanese Insurance Claims Database.

BackgroundMumps deafness causes serious problems, and incidence data are needed to identify its disease burden. However, such data are limited, and the reported incidence is highly variable. Nationwide studies in Japan with a large age range are lacking.MethodsThis was a retrospective observational investigation of the 2005–2017 mumps burden using employment-based health insurance claims data. Data were analyzed for 5,190,326 people aged 0–64 years to estimate the incidence of mumps deafness.ResultsOf 68,112 patients with mumps (36,423 males; 31,689 females), 102 (48 males; 54 females) developed mumps deafness—an incidence of 15.0 per 10,000 patients (1 in 668 patients). Fifty-four (52.9%) patients had mumps deafness in childhood (0–15 years), and 48 (47.1%) had mumps deafness in adolescence and adulthood (16–64 years); most cases occurred in childhood, the peak period for mumps onset. The incidence of mumps deafness per 10,000 patients was 73.6 in adolescence and adulthood, 8.4 times higher than the incidence of 8.8 in childhood (P < 0.001). In childhood, the incidence of mumps deafness was 7.2 times higher among 6–15-year-olds (13.8; 95% CI, 10.2–18.2) than among 0–5-year-olds (1.9; 95% CI, 0.6–4.5), and this difference was statistically significant (P < 0.001). No sex difference was observed.ConclusionsThe incidence of mumps deafness per 10,000 patients aged 0–64 years was 15.0 (1 in 668 patients). A secondary risk of deafness following mumps virus infection was identified not only for children, but also for adolescents and adults.

Longitudinal Characterization of the Mumps-Specific HLA-A2 Restricted T-Cell Response after Mumps Virus Infection.

Waning of the mumps virus (MuV)-specific humoral response after vaccination has been suggested as a cause for recent mumps outbreaks in vaccinated young adults, although it cannot explain all cases. Moreover, CD8+ T cells may play an important role in the response against MuV; however, little is known about the characteristics and dynamics of the MuV-specific CD8+ T-cell response after MuV infection. Here, we had the opportunity to follow the CD8+ T-cell response to three recently identified HLA-A2*02:01-restricted MuV-specific epitopes from 1.5 to 36 months post-MuV infection in five previously vaccinated and three unvaccinated individuals. The infection-induced CD8+ T-cell response was dominated by T cells specific for the ALDQTDIRV and LLDSSTTRV epitopes, while the response to the GLMEGQIVSV epitope was subdominant. MuV-specific CD8+ T-cell frequencies in the blood declined between 1.5 and 9 months after infection. This decline was not explained by changes in the expression of inhibitory receptors or homing markers. Despite the ongoing changes in the frequencies and phenotype of MuV-specific CD8+ T cells, TCRβ analyses revealed a stable MuV-specific T-cell repertoire over time. These insights in the maintenance of the cellular response against mumps may provide hallmarks for optimizing vaccination strategies towards a long-term cellular memory response.

The antiviral effect of catechins on mumps virus infection

• The inhibitory effect and its mechanism of catechins on mumps virus infection. • Epigallocatechin gallate shows the highest antiviral potency. • A galloyl group in catechins is an important factor for the strong antiviral effect. • The antiviral effect can result from inhibition of the viral fusion activity. Catechins have been known to possess antiviral effects against influenza A and B viruses through the inhibition of both the viral receptor binding and viral sialidase activities. Here, we examined the antiviral effect of catechins on mumps virus infection. The addition of epigallocatechin gallate (EGCG), gallocatechin gallate, epicatechin gallate, or catechin gallate simultaneously with the mumps virus infection of Vero cells greatly inhibited the infection. EGCG showed the strongest antiviral effect among the catechins tested. These catechins did not exhibit an inhibitory effect against the receptor binding and sialidase activities in the hemagglutinin–neuraminidase of the mumps virus, which was different from a known mechanism for influenza A and B viruses. By contrast, these catechins inhibited the viral fusion activity. Our results indicate that catechins are a useful food-derived antiviral agent against the mumps virus.

The incidence of mumps in Taiwan and its association with the meteorological parameters: An 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.

Mumps-Related Disease Burden in Japan: Analysis of JMDC Health Insurance Reimbursement Data for 2005-2017.

BackgroundMumps vaccination coverage is low in Japan, partly because of its voluntary nature. Although pediatric cases of mumps virus infection are captured by the National Epidemiological Surveillance of Infectious Diseases program under the Infectious Disease Law, there are currently no data regarding the occurrence of mumps and its complications in adults.MethodsWe investigated the annual incidence rates of mumps and its complications based on health insurance reimbursement data for 5,209,660 individuals aged 0–64 years for 2005–2017, obtained from JMDC Inc., to estimate the mumps-related disease burden during this period.ResultsThere were three mumps outbreaks (2006, 2010, and 2016) during 2005–2017. The annual incidence of mumps was highest in individuals aged 0–5 years (808–3,792 per 100,000 persons), followed by those aged 6–15 years (658–2,141 per 100,000 persons). The incidence of mumps was higher in females than in males (male/female ratio, 0.90). Among mumps-related complications, the overall incidence (per 1,000 mumps cases) was highest for orchitis (6.6), followed by meningitis (5.8), deafness (1.3), pancreatitis (0.5), and encephalitis (0.3). No cases of oophoritis were noted. The overall incidence of mumps-related complications was 2.5 times higher in males than in females.ConclusionsThis study revealed the disease burden due to mumps and its complications in Japan during 2005–2017. These data suggest the need for mumps-prevention measures in adolescents and adults, as well as in children.

Molecular identification and clinical characteristics of mumps virus and human herpesviruses associated with aseptic meningitis in South of Iran.

The online version contains supplementary material available at 10.1007/s13337-021-00718-y.

Seroprevalence of anti-mumps virus IgG antibody titer and voluntary mumps vaccination coverage in young adults in Japan

ABSTRACT In Japan, monovalent vaccine against mumps virus (MuV) infection was shifted to a voluntary basis vaccination due to the incidences of aseptic meningitis in the past. According to an analysis of a total of 409 participants aged 18–20 years, overall vaccination coverage rate was 48%. The mean anti-MuV IgG antibody titer of participants with medical history and more than two times vaccination was significantly higher than that in those without a medical history and unvaccinated and single vaccination, respectively. Seropositivity against MuV infection was >50% regardless of the number of vaccinations. Although these results suggest that seropositivity may persist due to asymptomatic infection, it is necessary to implement either a high vaccine coverage or routine vaccination for prevention of periodic mumps epidemics.

Mumps Orchitis: Clinical Aspects and Mechanisms.

The causative agent of mumps is a single-stranded, non-segmented, negative sense RNA virus belonging to the Paramyxoviridae family. Besides the classic symptom of painfully swollen parotid salivary glands (parotitis) in mumps virus (MuV)-infected men, orchitis is the most common form of extra-salivary gland inflammation. Mumps orchitis frequently occurs in young adult men, and leads to pain and swelling of the testis. The administration of MuV vaccines in children has been proven highly effective in reducing the incidence of mumps. However, a recent global outbreak of mumps and the high rate of orchitis have recently been considered as threats to male fertility. The pathogenesis of mumps orchitis remains largely unclear due to lack of systematic clinical data analysis and animal models studies. The alarming increase in the incidence of mumps orchitis and the high risk of the male fertility have thus become a major health concern. Recent studies have revealed the mechanisms by which MuV-host cells interact and MuV infection induces inflammatory responses in testicular cells. In this mini-review, we highlight advances in our knowledge of the clinical aspects and possible mechanisms of mumps orchitis.

Functional analysis of host factors involved in mumps virus propagation

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.

Clinical Profile and Outcome of Children with Acute Central Nervous System Infection in Kerala, India

Background and aims: Infection of the central nervous system is a significant cause of morbidity and mortality in children. The aim of this study was to evaluate clinical profile and outcome of children aged 1 month to 15 years admitted with acute central nervous system infection between 2008 and 2020 in the Department of Pediatrics, Ananthapuri Hospitals and Research Institute, Thiruvananthapuram, India. Materials and methods: This was a case record based retrospective study. Results: Of 62 children, 44 had meningitis and 18 had encephalitis. Most patients were in the age group 1-5 years old and males were the predominant sex (70.96%). Eighteen patients with meningitis had a clinical triad of fever, headache, and vomiting, while only three with encephalitis experienced this. Seizures and altered sensorium were seen significantly more in children with encephalitis. Cerebrospinal fluid pleocytosis was seen in significantly more patients with meningitis compared with patients with encephalitis. Aetiology for meningitis included pneumococcus, Orientia tsutsugamushi (scrub typhus), meningococcus, and Angiostrongylus cantonensis infection. Causes of encephalitis included enterovirus, mumps virus, herpes simplex virus, dengue virus, and H1N1 influenza virus infection. Paediatric intensive care unit admission was more common for patients with encephalitis. One child with pneumococcal meningitis and another with dengue encephalitis died. Seizures were the most common sequelae. Conclusion: Typical clinical features were not present in most patients with meningitis; therefore, a high index of suspicion is needed for early diagnosis. Exact aetiologies could not be identified in most of the patients. Pneumococcus, scrub typhus, and meningococcus were the aetiological agents identified for meningitis. Encephalitis was attributed to dengue virus, herpes simplex virus, enterovirus, mumps virus, and H1N1 influenza virus infection.

High Proportion of School Aged Children Susceptible to Mumps Virus Infections in the City of Mwanza, Tanzania: Should It be Included in the National Immunization Programme?

Aim: This study for the first time in Mwanza, Tanzania aimed at determining seropositivity of mumps virus in school aged children who are targeted for vaccination.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of the Study: This study was conducted in the city of Mwanza from July to September 2018.&#x0D; Despite being common with reported associated complications in many resource limited countries, there is scarcity of information on its epidemiology in Tanzania.&#x0D; Methodology: We enrolled 440 school children aged 6-12 years. Data was collected using a pre-tested structured data collection tool. Blood samples were collected, and sera were used for detection of mumps virus antibodies by indirect enzyme linked immunosorbent assay (ELISA). Data was analyzed using STATA version 13, 2013.&#x0D; Results: The median age of enrolled children was 9(IQR: 8-11) years. The seropositivity of mumps IgG antibodies was found to be 94(21.4%, 95% CI: 17.5-25.1) while that of IgM was 1 (0.23%, 95% CI: 0.02-0.6). By multivariable logistic regression analysis, residing in rural areas (OR: 2.28, 95% 1.42-3.36, P=0.001) and age &gt;10 years (OR: 1.67, 95% CI: 1.03-2.7, P=0.036) independently predicted mumps IgG seropositivity.&#x0D; Conclusion: A significant proportion of young children in urban areas of the city of Mwanza are susceptible to mumps virus infection indicating the need to generate more data across the country so as to institute appropriate control measures including measles, mumps and rubella (MMR) vaccination programme.