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Background: The re-emergence of mumps among vaccinated young adults has become a global issue. Besides waning of antibody responses, suboptimal induction of T-cell responses may reduce protection. In a recent study, we observed a dominant polyfunctional CD8+ T-cell response after natural mumps virus (MuV) infection that was not present after vaccination. Unraveling the MuV epitope repertoire can provide insight in the specificity, functionality, and breadth of the T-cell response against MuV., Methods: Peptides were eluted from human leukocyte antigen (HLA) class I molecules of MuV-infected cells and characterized by advanced mass spectrometry. Selected identified MuV peptides were tested for in vitro and ex vivo immunogenicity., Results: In this study, we identified a broad landscape of 83 CD8+ T-cell epitopes of MuV, 41 of which were confirmed based on synthetic peptide standards. For 6 epitopes, we showed induction of an HLA-A*02-restriced CD8+ T-cell response. Moreover, robust T-cell responses against 5 selected MuV epitopes could be detected in all tested mumps patients using peptide/HLA-A*02:01 dextramers., Conclusions: The identified CD8+ T-cell epitopes will help to further characterize MuV-specific T-cell immunity after natural MuV infection or vaccination. These MuV epitopes may provide clues for a better understanding of, and possibly for preventing, mumps vaccine failure.We identified for the first time 41 mumps virus (MuV)-specific HLA-A*02 epitopes. For 6 epitopes, CD8+ T-cell responses were confirmed in T cells derived from several mumps cases, and MuV-specific CD8+ T cells could be identified by peptide/dextramer staining., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Hydrocephalus is a rare and devastating complication of mumps encephalitis. The histopathological correlates of mumps infection in central nervous system tissues are not well-characterized. We present the case of a 54-year-old patient who suffered long-term neuropsychiatric sequelae and hydrocephalus as a consequence of a childhood mumps infection. Brain autopsy revealed significant dilation of the lateral and third ventricles. Aqueductal stenosis was not observed on premortem imaging or on gross examination. Histology revealed loss of ependymal epithelium throughout the aqueduct and ventricular system. Macrophage conglomerates were identified within the cerebral aqueduct at the level of the pons in addition to subjacent periaqueductal gliosis and scattered Rosenthal fibers. Together, these findings support primary ependymal injury as a pathophysiological mechanism in the development of chronic hydrocephalus following mumps infection. Finally, we review the existing literature and discuss potential mechanisms of disease., (© 2019 American Association of Neuropathologists, Inc. All rights reserved.)

Anaesthesia mumps is an uncommon postoperative complication resulting in unilateral or bilateral swelling of the parotid glands following surgical and endoscopic procedures. Our case illustrates the benign course of anaesthesia mumps in a postoperative vaginal hysterectomy patient with no underlying illness and also discusses previous cases in the literature and management strategies., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Mumps virus (MuV) has high tropism to the testis and may lead to male infertility. Sertoli cells are the major targets of MuV infection. However, the mechanisms by which MuV infection impairs male fertility and Sertoli cell function remain unclear. The present study elucidated the effect of MuV infection on the blood-testis barrier (BTB). The transepithelial electrical resistance of MuV-infected mouse Sertoli cells was monitored, and the expression of major proteins of the BTB was examined. We demonstrated that MuV infection disrupted the BTB by reducing the levels of occludin and zonula occludens 1. Sertoli cells derived from Tlr2 -/- and Tnfa -/- mice were analyzed for mediating MuV-induced impairment. TLR2-mediated TNF-α production by Sertoli cells in response to MuV infection impaired BTB integrity. MuV-impaired BTB was not observed in Tlr2 -/- and Tnfa -/- Sertoli cells. Moreover, an inhibitor of TNF-α, pomalidomide, prevents the disruption of BTB in response to MuV infection. FITC-labeled biotin tracing assay confirmed that BTB permeability and spermatogenesis were transiently impaired by MuV infection in vivo . These findings suggest that the disruption of the BTB could be one of the mechanisms underlying MuV-impaired male fertility, in which TNF-α could play a critical role.-Wu, H., Jiang, X., Gao, Y., Liu, W., Wang, F., Gong, M., Chen, R., Yu, X., Zhang, W., Gao, B., Song, C., Han, D. Mumps virus infection disrupts blood-testis barrier through the induction of TNF-α in Sertoli cells.

We report two cases of acute aseptic meningitis associated to mumps in middle-aged women, one pregnant. Both presented shortly after parotid gland enlargement. Neurological complications were suspected by headache, fever and meningeal signs and confirmed by CSF findings (mononuclear predominant pleocytosis) with negative results for alternative causes. Mumps were confirmed by positive IgM and IgG serology. Both patients were discharged with a favorable evolution and complete disappearance of symptoms. Cases were concurrent with a regional mumps outbreak. Conclusions: Aseptic meningitis is a rare mumps-associated neurological complication. Its diagnostic can be achieved by precedent parotid enlargement, mononuclear pleocytosis in the CSF and positive IgM and IgG serology or viral detection by PCR in urine or salivary samples. This complication would be more probably observed during mumps outbreaks.

Relation: Iodide mumps is an uncommon condition, induced by iodide-containing contrast, and is characterized by a rapid, painless enlargement of the bilateral or unilateral salivary gland. At present, the pathogenesis of iodide mumps is not yet clear. It may be related to an idiosyncratic reaction, a toxic accumulation of iodine in the gland duct, or renal function damage leading to an iodine excretion disorder. This paper reports the clinical manifestations and magnetic resonance imaging results of one case of iodide mumps, which occurred after digital subtraction angiography., Patient Concerns: A 66-year-old Chinese man presented to our department with a 1-month speech barrier and 1 day of vomiting. He had the history of high blood sugar, the history of high blood pressure and the history of Vitiligo. He had no history of allergies and had never previously received iodide-containing contrast. His renal function and other laboratory examinations were normal. During the digital subtraction angiography (DSA), the patient received approximately 130 mL of nonionic contrast agent (iodixanol). Five hours postsurgery, the patient experienced bilateral parotid enlargement with no other discomfort, such as pain, fever, skin redness, itching, hives, nausea, vomiting, or respiratory abnormalities., Diagnoses: We thought the diagnosis was iodide mumps., Intervention: Intravenous dexamethasone (5 mg) was administered., Outcome: 20 hours post-DSA, after which the bilateral parotid shrunk. By 4 days postsurgery, the patient's bilateral parotid had recovered completely., Lessons: We found no obvious abnormal sequence signal in diffusion magnetic resonance imaging or the corresponding apparent diffusion coefficient. Our findings suggest that vasogenic edema may play an important role in the pathogenesis of iodide mumps., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Mumps virus (MuV) infection usually results in germ cell degeneration in the testis, which is an etiological factor for male infertility. However, the mechanisms by which MuV infection damages male germ cells remain unclear. The present study showed that C-X-C motif chemokine ligand 10 (CXCL10) is produced by mouse Sertoli cells in response to MuV infection, which induces germ cell apoptosis through the activation of caspase-3. CXC chemokine receptor 3 (CXCR3), a functional receptor of CXCL10, is constitutively expressed in male germ cells. Neutralizing antibodies against CXCR3 and an inhibitor of caspase-3 activation significantly inhibited CXCL10-induced male germ cell apoptosis. Furthermore, the tumor necrosis factor-α (TNF-α) upregulated CXCL10 production in Sertoli cells after MuV infection. The knockout of either CXCL10 or TNF-α reduced germ cell apoptosis in the co-cultures of germ cells and Sertoli cells in response to MuV infection. Local injection of MuV into the testes of mice confirmed the involvement of CXCL10 in germ cell apoptosis in vivo. These results provide novel insights into MuV-induced germ cell apoptosis in the testis.

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.

Background: Mumps is a vaccine-preventable disease that usually occurs as a parotitis, but it can also lead to several life- threatening complications, including pancreatitis, meningitis and encephalitis., Objective: To determine and diagnosis of mumps disease, which is communicable disease usually affects childrens. Although it is seen worldwide, but outbreaks not common in India., Materials and Methods: Thirty one suspected mumps cases, who presented to the unimmunized population of Chikkahallivana village in Davangere district of Karnataka, India in January 2014, with clinical evidence of fever, cervical lymphadenitis and ear pain, manifest with self-limited uni-or bilateral parotitis. A total of 31 cases consisting of 31 blood and 31 throat swabs were tested for diagnosis of mumps disease., Results: Of the 31 suspected cases, laboratory results showed 18 positive for mumps IgM antibodies and 7 cases showed presence of mumps virus RNA by RT-PCR using MV specific nested primers. From 31 cases, 5 were positive with both the methods., Conclusion: We confirmed the cases by serological as well as a sensitive RT-nested PCR-based method and sequencing results for the molecular identification of mumps infection. Sequencing results of the SH gene identified outbreak strain as genotype C, which was consistent with other outbreaks in India.

Mumps is caused by the mumps virus (MuV), a member of the Paramyxoviridae family of enveloped, non-segmented, negative-sense RNA viruses. Mumps is characterized by painful inflammatory symptoms, such as parotitis and orchitis. The virus is highly neurotropic, with laboratory evidence of central nervous system (CNS) infection in approximately half of cases. Symptomatic CNS infection occurs less frequently; nonetheless, prior to the introduction of routine vaccination, MuV was a leading cause of aseptic meningitis and viral encephalitis in many developed countries. Despite being one of the oldest recognized diseases, with a worldwide distribution, surprisingly little attention has been given to its study. Cases of aseptic meningitis associated with some vaccine strains and a global resurgence of cases, including in highly vaccinated populations, has renewed interest in the virus, particularly in its pathogenesis and the need for development of clinically relevant models of disease. In this review we summarize the current state of knowledge on the virus, its pathogenesis and its clinical and pathological outcomes., (Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

In recent years, large mumps outbreaks, involving mainly adolescents and young adults, have re-emerged in several countries. We investigated a large mumps outbreak, evaluated the association between mumps clinical severity (complications, hospitalization) and vaccination status (number of previous measles, mumps and rubella - MMR vaccine doses), and assessed vaccine effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in Jerusalem and were epidemiologically linked to the mumps outbreak in New York. Overall, 3130 mumps cases were notified in the Jerusalem district during September 2009-August 2011 (median age 13y, 64% males). Most cases were reported from community clinics. Patients with systemic symptoms and/or complications (419, 13.4%) were either hospitalized (n = 79) or treated in an emergency medical center (n = 340). The main complications included orchitis (3.8% males> age 12y) and meningoencephalitis (0.5%). The mumps virus genotype was G5. The distribution of previous MMR vaccine doses (n = 0,1,2) was: 24.8%, 28.3% and 46.9%, respectively. The number of previous vaccine doses was inversely associated with clinical severity. Adjusted values for MMR vaccine effectiveness against complications were estimated as 52.1% (95% CI -4 -78%) for one vaccine dose and 62.7% (95% CI 25.7-81.3%) for 2 doses. The outbreak was characterized by predominance of male students; the majority of whom had been previously vaccinated. The reported complication rate was relatively low. Vaccination status was associated with age and disease severity. The combination of limited mumps vaccine effectiveness and the specific school setting (dense learning and living conditions) probably contributed to the disease spread.

We present a case of mumps orchitis after vaccination. A 35-year-old man visited the emergency unit of our hospital for fever and right testicular pain on 7 January 2012. Two weeks before the visit, he underwent vaccination for mumps. After 7 days of hospitalization, the patient recovered from fever and testicular pain. Scrotal magnetic resonance imaging suggested right orchitis, and an increased level of serum mumps immunoglobulin M and immunoglobulin G indicated an initial infection of mumps virus. The peak value of immunoglobulin G showed 106 enzyme immunoassay unit 5 weeks after vaccination, which was 10-fold higher than the ordinary rise of a vaccinated individual. This fact leads to two possibilities. One is this happened as an adverse event of vaccination, and the other is that he actually had a wild-type infection at the same time as vaccination. There are some reports regarding adverse events of mumps vaccine; however, they might include wild-type infection., (© 2013 The Japanese Urological Association.)

Mumps-associated hemophagocytic syndrome (HPS) is exceptionally rare. Here, we report a fatal case of concurrent mumps and HPS. A previously healthy 21-year-old male patient was admitted to the Department of Infectious Diseases on October 18, 2011,with complaints of parotid gland pain for 30 days and persistent fever (38.3°C-40°C) for 15 days. Admission examinations showed severe pancytopenia, liver dysfunction, hyperferritinemia, fibrinopenia, elevated lactalase dehydrase, bilateral pulmonary inflammation and pleural effusion, abdominal lymphadenopathy, and splenomegaly. The patient was accordingly suspected to have mumps-associated HPS and received nutrition support and hormonal therapies as well as platelet transfusions. On hospitalization day 3, the fever stayed high, and painful swelling in the right testicle was reported. A bone marrow biopsy evaluation and serological tests were then performed. Histiocytic hyperplasia and hemophagocytic macrophage infiltration were demonstrated in the bone marrow and antimumps virus immunoglobulin M was detected positive, but bacteria, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus were detected negative in the peripheral blood. The initial diagnosis of mumps-associated HPS was eventually confirmed. Treatments with high doses of methylprednisolone, intravenous immunoglobulin, and etoposide were continued. By hospitalization day 20, patient's condition was improved, his body temperature and blood counts were almost normal, and the pain and swelling in his parotid glands and right testicle subsided considerably. On hospitalization day 28, however, patient's condition deteriorated rapidly, and pancytopenia became evident again. On hospitalization day 33, the patient died of multiple organ dysfunction.

This article provides a review of the epidemiological data on mumps in France since 1986. The results of 26 years of monitoring in general practice by the Sentinel network are analysed, such as hospitalisation data between 2004 and 2010, as well as mortality data between 2000 and 2009. The annual incidence rate has plummeted between 1986 and 2011, from 859 cases per 100,000 inhabitants [95% CI: 798-920] to 9 cases per 100,000 inhabitants [95% CI: 4-14]. A change in the age distribution is significant with an increase of Relative Illness Ratio (RIR) for patients over 20 years. Since 2000, vaccine status has also changed, and the majority of recent mumps cases occur among previously vaccinated patients. The average annual hospitalisation rate is 3.2 per 1 million inhabitants. Mumps was identified as the initial cause of death in 1 case every 5 years. This study estimates the burden of mumps disease in France., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Mumps epidemics are usually caused by airborne transmission of mumps virus (MuV) and have high morbidity in non-immunized children. Epidemiological studies in many regions of China show that the genotype F viral strain is the most prevalent. However, the genotype A strain is currently used to prepare vaccines. Regional epidemiological MuV data suggest a significant application for the development of live attenuated mumps vaccines targeting specific genotypes. This article reports the isolation and culture of a genotype F MuV candidate strain that could be used to prepare a live attenuated mumps vaccine. This strain is shown to have good immunological efficacy and stability in neurovirulence evaluations. This work should facilitate the implementation of mumps vaccination in mainland China by targeting the most prevalent MuV genotype, genotype F., (Copyright © 2010 Institut Pasteur. Published by Elsevier SAS. All rights reserved.)

To determine how long people shed virus after the onset of mumps, we used logistic regression modeling to analyze data from the 2006 outbreak of mumps in Iowa. Our model establishes that the probability of mumps virus shedding decreases rapidly after the onset of symptoms. However, we estimate that 8%-15% of patients will still be shedding the virus 5 days after the onset of symptoms and, thus, may still be contagious during this period.

Mumps virus is highly neurotropic, with evidence of infection of the central nervous system in more than half of clinical cases. In the prevaccine era, mumps was a major cause of viral meningitis in most developed countries. Despite efforts to attenuate the virus, some mumps vaccines have retained virulence properties and have caused aseptic meningitis in vaccinees, resulting in public resistance to vaccination in some countries. Ensuring the safety of mumps vaccines is an important public health objective, as the need for robust immunization programs has been made clear by the recent resurgence of mumps outbreaks worldwide, including the United States, which in 2006 experienced its largest mumps outbreak in 20 years. To better understand the molecular basis of mumps virus attenuation, the authors developed two infectious full-length cDNA clones for a highly neurovirulent strain of mumps virus. The clones differed at only one site, possessing either an A or G at nucleotide position 271 in the F gene, to represent the heterogeneity identified in the original virulent clinical isolate. In comparison to the clinical isolate, virus rescued from the A-variant cDNA clone grew to higher cumulative titers in vitro but exhibited similar cytopathic effects in vitro and virulence in vivo. In contrast, virus rescued from the G-variant cDNA clone, in comparison to the clinical isolate and the A-variant, was more fusogenic in vitro but replicated to lower cumulative titers and was less neurovirulent in vivo. These data suggest that nucleotide position 271 in the F gene plays a significant role in virus pathogenesis. This infectious clone system will serve as a key tool for further examination of the molecular basis for mumps virus neurovirulence and neuroattenuation.

Mumps is a world-wide distributed human infectious disease. The causative agent is mumpsvirus, a single-stranded RNA virus belonging to the Paramyxoviridae. Mumpsvirus causes a variety of illnesses, which depend in part on humans' age and sex. Parotitis and meningitis as well as respiratory tract infection in children and orchitis in pubertal and postpubertal males are very common. Asymptomatic infections have also been frequently described. The treatment for mumps infection is symptomatic, there is no specific antiviral therapy. Immune prophylaxis with an attenuated life vaccine is the most important strategy of mumps prevention. During the last years, an increased number of mumps cases have been observed in several countries with a general recommendation for mumps vaccination. Young adults have been most frequently affected. The lack of immunity in this population is likely to be responsible for the increasing number of mumps cases.

Adhesion molecules play a key role in leucocyte migration into the central nervous system (CNS). Concentrations of endothelial-derived soluble intercellular adhesion molecule-1 (sICAM-1) and leucocyte-originated soluble L-selectin (sL-selectin) in cerebrospinal fluid (CSF) of children with mumps meningitis (mononuclear pleocytosis, n = 33) and mumps (absence of pleocytosis, n = 9) were compared with values from age-matched control group (n = 19). In 14 patients from the meningitis group, adhesion molecule levels together with albumin concentration were estimated in paired CSF/serum samples to calculate concentration quotients and determine molecule intrathecal release. Both sICAM-1 (median 3.44 versus 0.86 ng/ml; P < 0.0001) and sL-selectin (median 29.91 versus 8.52 ng/ml; P < 0.0001) concentrations in CSF were increased in mumps meningitis patients compared with controls. Increased levels of the selected adhesion molecules were also observed in mumps patients without CNS involvement when compared with controls (median sICAM-1: 1.14 versus 0.86 ng/ml, sL-selectin: 13.54 versus 8.52 ng/ml; P < 0.01). Additionally, the concentration of adhesion molecules was found to correlate with CSF leucocyte count. Considerable correlation of sICAM-1 and sL-selectin quotients and corresponding albumin quotients suggests that a majority of the soluble adhesion molecules originated from the bloodstream. Analysis of adhesion molecule levels demonstrated indirect evidence of brain-derived fractions. Our results suggest the involvement of adhesion molecules during the early phase of mumps meningitis.

Mumps was diagnosed in an 11-year-old girl with bilaterally swollen cheeks. She had received mumps-measles-rubella vaccine as an infant.

Mumps virus is highly neurotropic and, prior to widespread vaccination programs, was the major cause of viral meningitis in the United States. Nonetheless, the genetic basis of mumps virus neurotropism and neurovirulence was until recently not understood, largely due to the lack of an animal model. Here, nonneurovirulent (Jeryl Lynn vaccine) and highly neurovirulent (88-1961 wild type) mumps virus strains were passaged in human neural cells or in chicken fibroblast cells with the goal of neuroadapting or neuroattenuating the viruses, respectively. When tested in our rat neurovirulence assay against the respective parental strains, a Jeryl Lynn virus variant with an enhanced propensity for replication (neurotropism) and damage (neurovirulence) in the brain and an 88-1961 wild-type virus variant with decreased neurotropic and neurovirulent properties were recovered. To determine the molecular basis for the observed differences in neurovirulence and neuroattenuation, the complete genomes of the parental strains and their variants were fully sequenced. A comparison at the nucleotide level associated three amino acid changes with enhanced neurovirulence of the neuroadapted vaccine strain: one each in the nucleoprotein, matrix protein, and polymerase and three amino acid changes with reduced neurovirulence of the neuroattenuated wild-type strain: one each in the fusion protein, hemagglutinin-neuraminidase protein, and polymerase. The potential role of these amino acid changes in neurotropism, neurovirulence, and neuroattenuation is discussed.

Viral infection modulates the regulation of apoptosis in host cells. Here, we report a novel mechanism by which human cells infected with mumps virus become susceptible to apoptosis caused by extracellular stresses. Mumps virus stimulates proteasome-dependent degradation of STAT-1 by action of viral accessory protein V, resulting in a severe decrease in STAT-1 protein in infected cells. We exposed mumps virus-infected and uninfected cells to heat and chemical stress. The infected cells failed to acquire resistance to apoptotic stimuli (thermotolerance) after exposure to these mild stresses. The induction of HSP27 by stress exposure was dramatically suppressed in the infected cells, but HSP70 induction was not affected. STAT-1 was required for transcriptional activation of the HSP27 gene, but not for the HSP70 gene, and cDNA transfection of STAT-1 in mumps virus-infected cells restored thermotolerance. Phosphorylated heat shock factor-1 (HSF-1) and STAT-1 phosphorylated on neither tyrosine nor serine residues were co-transported to the nucleus in response to stress. Furthermore, overexpression of unphosphorylatable mutants of STAT-1 also restored thermotolerance in mumps virus-infected cells. These lines of evidence indicate that the induction of HSP27 by stress requires STAT-1 in addition to the activated HSF-1. Furthermore, STAT-1 required for the induction of HSP27 worked independent to its phosphorylation. Thus, HSP27-dependent thermotolerance is suppressed by mumps virus infection through the destruction of STAT-1. The lack of thermotolerance should allow the infected cells to be eliminated by apoptosis and might be a host defense against viral infection.

Background: Surprisingly little is known about the interactions between viruses and the male uro-genital tract. These are important, as viral testicular orchitis, induced by mumps or human immunodeficiency virus (HIV) infection for example, can lead to sterility. Moreover, semen is an essential vector in the propagation of sexually transmissible viral diseases. Here, we studied the effects of testicular infection with Sendai virus, a virus related to mumps virus, on the cellular distribution of viral particles and on testicular morphology, with particular attention to the testicular leukocyte population., Methods: At 5, 9, 11 or 24 h post-injection of Sendai virus through the scrotum, the testes were fixed for morphological and immunohistological studies. Localization of virus particles and numeration of leukocytes were performed using specific antibodies and morphological criteria., Results: As early as 5 h post-injection, a rapid and massive infiltration of leukocytes was observed in the interstitial tissue. The peritubular cell layer and the most external part of the basal portion of the seminiferous tubules were altered. The virus was diffusely located within the interstitial tissue 9 h following the injection whereas, after 24 h, viral proteins were restricted to the cytoplasm of infiltrated leukocytes. The number of leukocytes increased with time post-injection. Thus, 24 h post-injection, CD3+ T-cell number was 3-fold higher, ED1+ monocyte number was 4-fold higher and polynuclear cell number was 600-fold higher than in the control testes (P<0.001 all observations). In contrast, the population of resident macrophages was unaffected by Sendai virus., Conclusions: Testicular viral infection causes inflammation including rapid recruitment of leukocytes. The experiments presented here provide a model for further studies on the etiopathology of viral orchitis, in particular that caused by mumps virus.

Structural changes and functional features of the testes were studied in 20 patients who had had parotid orchitis (PO) 6 months to 1.5 years before the study. The examination including ultrasonography of the testes, investigation of ejaculate, radioimmunoassay for serum testosterone, FSH, LH brought out a significant reduction of the mean volume and echogenicity of the affected testicles by 44.7 and 50%, respectively, in 15 patients; a 58.2% decrease in the number of spermatozoa in ml; a 71.2% rise in FSH level in 6 patients. Morphometry of biopsy specimen of the testicles on the affected side has shown that mean sectional area of the tubules has diminished by 40%, the spermatogenesis index--by 77.1% while the volume of the intertubular connective tissue increased by 47.7%. Thus, after acute PO, the patients develop atrophic changes in the testes and a decline in spermatogenic function up to secretory infertility.

The neurovirulence of two mumps virus strains was compared using marmosets. Marmosets were inoculated intravenously with the wild-type mumps virus Odate strain, resulting in evident meningitis in 1 of 3 marmosets at each of the weeks 3, 4, and 5 postinoculation, representing a total of 3 out of 9 marmosets. Nephritis, parotitis, pancreatitis, and tonsillitis were manifest in addition to central nervous system (CNS) sequelae. On the other hand, the Jeryl Lynn vaccine strain did not induce histopathological changes in the CNS and multiplication of the Jeryl Lynn strain was distinctly lower compared to that of the Odate strain in the marmoset. This is the first report to describe the induction of meningitis in non-human primates after peripheral inoculation of a wild-type mumps virus, presenting findings useful for the elucidation of the mechanism of infection and pathology of mumps virus in the CNS. The distinction observed between the Odate and Jeryl Lynn strains suggests the applicability of the marmoset model for the evaluation of any neurovirulence potential of vaccine strains., (Copyright 2002 Wiley-Liss, Inc.)

Four levels (types) of immune response, differing by expression of cytokines (TNF-alpha, IL-1 beta, IL-4, and gamma-IFN) and immunoglobulins IgG2, IgG3, IgG4, and IgE) and by expression and time course of specific cell-mediated and humoral immune response, were detected in children with different clinical forms of mumps. Types 1 and 3 immune response are predominantly cell-mediated, while types 2 and 4 predominantly humoral during the acute phase of the disease. The cytokine and antigen-specific profiles of each type of immune response correlate with the severity of clinical course of mumps.

Background and Aim: There is controversy regarding whether paramyxovirus infection is causally associated with inflammatory bowel disease (IBD). The latest cohort study claimed that atypical measles and mumps infections in childhood may be risk factors for later IBD. This study was conducted to clarify the validity of a causal link between persistent mumps virus infection and IBD., Subjects and Methods: (1) Amplification of the mumps virus genome was performed in both intestinal specimens (ulcerative colitis 15, Crohn's disease 15, control 10) and peripheral blood lymphocytes (PBL) (ulcerative colitis seven, Crohn's disease six, control three) by reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern hybridisation using primers specific to the viral genome encoding phosphoprotein or haemagglutinin-neuraminidase. (2) Titre of serum antimumps IgG was measured in 16 patients with ulcerative colitis, in 16 patients with Crohn's disease, and in 16 normal controls using an enzyme linked immunosorbent assay., Results: (1) The mumps virus genome was not detected by RT-PCR in intestinal specimens or PBL in any case. (2) Antimumps IgG titre was positive in 7/16 ulcerative colitis, 10/16 Crohn's disease, and 11/16 control specimens. The mean (SEM) titre of antimumps IgG was 12.281 (7.831) in ulcerative colitis, 7.675 (1.608) in Crohn's disease, and 8.637 (1.969) in controls, with no significant difference between the three groups., Conclusion: We could not find any evidence to support a causal link between persistent mumps virus infection and IBD.

In order to elucidate the relationship between virus neurotropism and neuronal maturity, two experiments were performed. First, mumps virus infectivity was compared among the different developmental stages of hamster brains inoculated with mumps virus by examining the immunohistochemical distribution of mumps virus antigen. Second, brain lesions resulting from mumps virus infection during the period of neuronal migration were histologically and ultrastructurally analyzed. Three groups of Syrian hamsters, Group E12 (fetuses on the 12th day of gestation), and Groups P2 and P30 (2 and 30 days old, respectively), were injected with mumps virus intraplacentally or intracerebrally. In Group P30, mumps virus antigen was observed specifically in ependymal cells and the choroid plexus. In addition to these areas, in Group P2, some neurons in layers II and III of the cerebral cortex also showed virus antigen immunoreactivity. In Group E12, mumps virus antigen accumulated primarily in the neuroepithelial cells within the ventricular zone. Neither specific intranuclear changes related to viral replication nor the formation of complete virions and nucleocapsids was observed. We conclude that mumps virus neurotropism to hamster brains is dependent on the degree of neuronal maturity and that mumps virus can induce an abortive infection and resultant neuronal cell necrosis in the immature developing hamster brain.

Wild type mumps viruses are highly neurotropic and a frequent cause of aseptic meningitis in unvaccinated humans. To test whether attenuated mumps viruses used in the manufacture of mumps vaccines have neurovirulent properties, a monkey neurovirulence safety test (MNVT) is performed. However, results with several mumps virus MNVTs have raised questions as to whether the test can reliably discriminate neurovirulent from nonneurovirulent mumps virus strains. Here, various mumps virus strains representing a wide range of neuropathogenicity were tested in a standardized MNVT. A trend of higher neurovirulence scores was observed in monkeys inoculated with wild type mumps virus versus vaccine strains, although differences were not statistically significant. Results indicated the need for further examination and refinement of the MNVT or for development of alternative MNVTs.

Central nervous system susceptibility to viral infection is often age dependent for unclear reasons. In this study, we examined the age-dependent susceptibility of the brain in mumps virus-induced hydrocephalus in hamsters, and evaluated the relationship between neuropathologic features and brain barriers using glial fibrillary acidic protein and zonula occludentes 1 (ZO-1) immunohistochemistry. In a group intracerebrally inoculated with mumps virus at 2 days of age, pathologic findings such as periventricular edema, ependymal cell loss, and ventricular dilation were more prominent and the distribution of mumps virus antigen was wider than in a group inoculated at 30 days of age. ZO-1-immunoreactive tight junctions in the hydrocephalic brains of the 2-day group were severely damaged in the choroid plexus and ependyma, and in white matter capillaries as early as 3 days after inoculation. These changes were not apparent in the hydrocephalic brains of the 30-day group. Prominent cortical dissemination of virus in the 2-day group was related to underdeveloped perivascular glial foot processes in brain parenchyma. Periventricular edema in the 2-day group was linked to ependymal and blood-brain barrier tight-junction permeability. Our results suggest that tight junctions in the early postnatal period are more immature and fragile than in the adult. We concluded that brain susceptibility in mumps virus-induced hydrocephalus is intimately related to the maturity of brain barriers.

Fourier analysis of in vivo human corneal endothelial cell structure was investigated using specular photomicrographs for a range of ages from less than one year to over 70. The theoretical basis for this analysis was investigated using mathematical models of cell structures where the elements determining their form could be modified in a controlled and quantified manner. The resulting Fourier transform properties were related to properties of cell structure. The experimental factors underlying this analysis were then studied using digitized images of corneal endothelial cells. It was found that the Fourier transforms provided quantitative descriptions of population cell size and organisation. For the smaller, more regular cell structure from the younger eyes, the expected larger rings of the Fourier transforms were demonstrated. Specular photomicrographs of older eyes gave rise to smaller diameter rings in their Fourier transforms. These results are consistent with the previous studies which used manual tracings of human endothelial cell patterns. This is the first demonstration of the direct Fourier analysis of clinical human corneal specular photomicrographs.

A simple and sensitive method was developed for the differentiation of the Hoshino vaccine strain from wild strains with a restriction fragment length polymorphism (RFLP) analysis in the part of hemagglutinin-neuraminidase (HN) gene. The virus genome was amplified by using a reverse transcriptase-polymerase chain reaction (RT-PCR) directly from clinical samples. The PCR product of the Hoshino vaccine strain was cleaved into 2 fragments after digestion with Sca I and Afl II. All wild strains showed 2 RFLP profiles, A and B, different from that of vaccine strain. Wild A strains were cut into 2 fragments after digestion with Sca I only, while wild B strains were cleaved neither with Sca I nor Afl II. This molecular approach provides an effective method for differentiation of the Hoshino vaccine strain from wild strains of mumps virus in patients after vaccination.

The reverse transcription/polymerase chain reaction (RT-PCR) was used to amplify a 129-bp fragment of the mumps virus F gene from strains circulating in the Siena area from 1993-1995. The nucleic acid was amplified directly from the samples; no growth in cell culture was required. Nucleotide sequence analysis and the comparison with other virus strains enabled the typing of the detected viruses. There appears to be more than one lineage of mumps virus circulating at any given time in the same location. A PCR assay coupled with the sequencing of the 5' end of the F gene seems to be a convenient method for characterizing mumps virus strains. This method, useful in diagnosis, also appears to be suitable for epidemiological studies.

We sought to elucidate the pathogenesis of Chiari type I malformation using an experimental model of hydrocephalus produced by inoculating hamsters with mumps virus. Dilatation of the lateral ventricules was detected in all brains inoculated at 2, 10, and 25 days of age. The cerebellum in hamsters inoculated at 2 and 10 days of age showed elongation and flattening of the vermis and protrusion or notching of the uvula. All layers, i.e., the molecular, Purkinje cell, and granular layers, and the white matter were preserved, but had become narrow. Purkinje cells remained normal. Hamsters inoculated at 25 days of age did not develop the cerebellar deformity. Mumps virus antigen was detected in all ependymal cells and in some epithelial cells of the choroid plexus in all hamsters that had been inoculated at 2, 10, or 25 days of age. Results suggest that Chiari type I malformation is caused by two main factors occurring simultaneously, i.e., increasing intracranial pressure and rapid histogenesis of the cerebellar cortex.

To elucidate the pathogenesis of early ventricular dilatation in hydrocephalus, we examined early morphological changes in ependymal layers at the lateral ventricles in suckling hamsters without aqueductal stenosis 5 days after the intracerebral inoculation of mumps virus. Mumps virus antigen was detectable in all ependymal cells. The ependymal cilia had almost disappeared and only the microvilli remained. A number of supraependymal cells were also observed on the surface of the lateral ventricles. Transmission electron microscopy revealed intracytoplasmic viral-like inclusions in the infected ependymal cells. These results suggest that functional and morphological disturbances in infected ependymal cells may cause early ventricular dilatation before aqueductal stenosis occurs.

A 5-year-old male patient with asymptomatic optic neuritis and mumps postinfectious encephalitis or acute disseminated encephalomyelitis is reported. Magnetic resonance imaging (MRI) with a short inversion time inversion recovery sequence was valuable in detecting clinically silent lesions of the unilateral right optic nerve in addition to visual evoked potentials. Evidence of concurrent optic neuritis was useful for detecting more extensive neurological involvement, leading to the diagnosis of mumps postinfectious encephalitis. A systematic MRI study should be performed in children with mumps encephalitis, regardless of appreciable clinical deficits.

Mumps virus caused a partially lytic infection in cultivated rat embryonic dorsal root ganglion neurons with a restricted formation of viral components. The neuronal degeneration was markedly enhanced by increasing the calcium concentration of the medium and could be almost totally inhibited by the dihydropyridine calcium channel antagonist nifedipine. The drug had no effect on a productive and completely lytic Sendai virus infection of the neurons. A previous neurophysiological study has shown that a reduced calcium influx occurs during the action potential early during the infection. The present study suggests a crucial role of calcium in neurodegeneration induced by certain viruses.

Renal cell carcinoma cells produced the substance(s) which killed them (suicide factor(s)) after co-culture with mumps virus. The suicide factor(s) were heat-sensitive and were degraded with trypsin. Furthermore, actinomycin D inhibited the production of the substance(s) by cancer cells. Considering these facts, the substance(s) were thought to be protein(s) derived from de novo synthesis in cancer cells. It was demonstrated that renal cell carcinoma cells proliferated with the autocrine loop of interleukin-6 (IL-6). Mumps virus almost completely inhibited the IL-6 production in several hours. Because of these two facts, the suicide process might be initiated in renal cell carcinoma cells after encountering mumps virus, i.e. inhibition of the autocrine growth loop of IL-6 followed by the induction of an autocrine killing loop of unknown substance(s).