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Surveillance of viral respiratory tract infections over a one year period in mainly hospitalized Austrian infants and children by a rapid enzyme-linked immunosorbent assay diagnosis.

In order to obtain more information on viral respiratory tract infections in Austrian infants and children, nasopharyngeal secretions from 1432 infants and children, collected from October 1984 to October 1985, were screened for the presence of respiratory syncytial virus (RSV), adenoviruses, parainfluenza virus type 1, 2, and 3, and influenza viruses type A and B, by enzyme-linked immunosorbent assay (ELISA). The results obtained were analyzed with respect to incidence, seasonal distribution and clinical syndromes associated with the different viral pathogens investigated and also with the practicability of ELISA diagnostics over long distances. A viral etiology of acute respiratory tract infection was confirmed in 372 (26%) infants. RSV was detected in 286 (20%) of the nasal secretions and was thus the most frequently encountered agent. RSV infections occurred mainly in the winter months and were often associated with bronchitis, bronchiolitis, and pneumonia. Only sporadic infections were found with one of the other viruses investigated.

Adenoviruses, Human↗

Clinical role of respiratory virus infection in acute otitis media.

The clinical characteristics of acute otitis media in relation to coexisting respiratory virus infection were studied in a 1-year prospective study of 363 children with acute otitis media. Respiratory viruses were detected using virus isolation and virus antigen detection in nasopharyngeal specimens of 42% of the patients at the time of diagnosis. Rhinovirus (24%) and respiratory syncytial virus (13%) were the two most common viruses detected. Adenovirus, parainfluenza viruses, and coronavirus OC43 were found less frequently. The mean duration of preceding symptoms was 5.9 days before the diagnosis of acute otitis media. Ninety-four percent of the children had symptoms of upper respiratory tract infection. Fever was reported in 55% and earache in 47% of cases. Patients with respiratory syncytial virus infection had fever, cough, and vomiting significantly more often than patients with rhinovirus infection or virus-negative patients. No significant differences were found in the appearance of the tympanic membrane and outcome of illness between virus-negative and virus-positive patients with acute otitis. Most patients respond well to antimicrobial therapy despite the coexisting viral infection. If the symptoms of infection persist, they can be due to the underlying viral infection, and viral diagnostics preferably with rapid methods may be clinically useful in these patients.

Acute Disease↗

The frequency, distribution and effects of antibodies, to seven putative respiratory pathogens, on respiratory disease and weight gain in feedlot calves in Ontario.

During 1983-85, 279 calves requiring treatment for bovine respiratory disease and 290 comparison (control) animals from 15 different groups of feedlot calves were bled on arrival and again at 28 days postarrival. Their sera were then analyzed for antibodies to seven putative respiratory pathogens. On arrival, the prevalences of indirect agglutination titers to Pasteurella haemolytica, P. haemolytica cytotoxin, Mycoplasma bovis and M. dispar were greater than 50%, the prevalence of titers to bovine virus diarrhea virus (BVDV) was approximately 40%, and the prevalences of titers to infectious bovine rhinotracheitis virus (IBRV), bovine respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) were all below 25%. Seroconversion during the first month after arrival occurred in more than half the calves to P. haemolytica cytotoxin, PIV3 and RSV. Seroconversion of agglutination titers to P. haemolytica, Mycoplasma and BVDV occurred in about 40% of calves, and seroconversion to IBRV was infrequent (less than 5%). Initial titers were negatively correlated to subsequent titer changes within organism. Initial titers, and titer changes between organisms were essentially independent. Light calves had an increased risk of being selected for treatment for respiratory disease. Seroconversion to P. haemolytica cytotoxin, RSV and BVDV were predictive of respiratory disease cases, explaining approximately 69% of all respiratory disease cases in the feedlots. It was not possible to accurately predict weight gain or relapse from the serological data.

Animals↗

Viral agents of acute respiratory infections in young children in Kuala Lumpur.

The results of this study indicate that the important viral agents associated with lower respiratory tract infections in young children are respiratory syncytial virus, rhinovirus, and parainfluenza virus, particularly in those under 2 years of age. This is in close agreement with studies done in temperate climates. Influenza A virus is seasonal and plays an important role in upper respiratory tract infections in older children.

Acute Disease↗

[Role of viral infections in acute exacerbation of idiopathic interstitial pneumonia].

To evaluate the possibility that viral infections can trigger acute exacerbations of idiopathic interstitial pneumonia (IIP), we analyzed data from 105 patients with IIP. Acute exacerbation was defined as an increase in dyspnea, a decrease in PaO2 by more than 10 Torr, and worsening of chest radiographic findings within one month. Viral infection was said to be involved when patients had more than a 4-fold change in viral antibody titer or viral inclusion bodies in sputum during the acute exacerbation. Of the 105 patients with IIP, 30 had acute exacerbations. Among these 30 patients, viral infection was said to be involved in 11 (37%). Presumptive viruses were influenza virus (n = 6), parainfluenza virus (n = 1), herpes simplex virus (n = 1), RS virus (n = 1), and cytomegalovirus (n = 2). The levels of serum immunoglobulin A (IgA) before acute exacerbations were significantly lower (p < 0.05) in patients in whom viral infection was said to be involved. These results suggest that viral infection associated with a low value of serum IgA is an important trigger of acute exacerbations of IIP.

Aged↗

Incidence of Mycoplasma pneumoniae, Chlamydia trachomatis, and viral infections in pneumonia cases under six months of age, Bangkok, Thailand.

The incidence of infections by Mycoplasma pneumoniae, Chlamydia trachomatis and respiratory viruses was investigated in 76 pneumonic patients aged under 6 months who attended Ramathibodi and Siriraj Hospitals in Bangkok during two study periods. M. pneumoniae infection was not found in any case from either hospital by serological diagnosis. By the isolation method, C. trachomatis infection was found in 7(16.7%) of 42 patients from Ramathibodi Hospital and 5(21.7%) of 23 patients from Siriraj Hospital with the average male:female ratio of 2.6:1; and 91.7% of the infected cases were under 3 months old. Laboratory diagnosis of respiratory virus infection was performed by indirect immunofluorescence (IIF), isolation, and by antibody detection. Data from Ramathibodi Hospital showed that 11 (24.4%), 4 (8.9%), 3 (6.7%) of the 45 patients were infected by respiratory syncytial virus (RSV), adenoviruses, parainfluenza virus type 3, and some other viruses, respectively; infection rates of 10 (32.3%), 4 (12.9%), 1 (3.2%) and 1 (3.2%) by those viruses respectively, were observed in the 31 patients from Siriraj Hospital.

Chlamydia Infections↗

STAT2 acts as a host range determinant for species-specific paramyxovirus interferon antagonism and simian virus 5 replication.

The antiviral state induced by alpha/beta interferon (IFN-alpha/beta) is a powerful selective pressure for virus evolution of evasive strategies. The paramyxoviruses simian virus 5 (SV5) and human parainfluenza virus 2 (HPIV2) overcome IFN-alpha/beta responses through the actions of their V proteins, which induce proteasomal degradation of cellular IFN-alpha/beta-activated signal transducers and activators of transcription STAT1 and STAT2. SV5 infection induces STAT1 degradation and IFN-alpha/beta inhibition efficiently in human cells but not in mouse cells, effectively restricting SV5 host range. Here, the cellular basis for this species specificity is demonstrated to result from differences between human and murine STAT2. Expression in mouse cells of full-length or truncated human STAT2 cDNA is sufficient to permit antagonism of endogenous murine IFN-alpha/beta signaling by SV5 and HPIV2 V proteins. Furthermore, virus-induced STAT protein degradation is observed in mouse cells only in the presence of ectopically expressed human STAT2. The results indicate that STAT2 acts as an intracellular determinant of paramyxovirus host range restriction, which contributes to the species specificity of virus replication, and that human STAT2 can confer a growth advantage for SV5 in the murine host.

3T3 Cells↗

[Pathogenesis of congenital hydrocephalus: role of transplacental myxovirus infection].

Several pediatric cases of hydrocephalus after mumps virus infection, have been reported. These cases are thought to be caused by ependymitis due to mumps virus infection. Clinical cases of congenital hydrocephalus possibly caused by intrauterine mumps virus infection are also accumulating. However, it has not yet been made clear whether mumps virus can pass through the human placenta and cause hydrocephalus. Our experimental studies demonstrated that mumps and parainfluenza virus type 3 could induce hydrocephalus by destructive ependymal infection in suckling hamsters, when they were inoculated intracerebrally or intraperitoneally. However, the transplacental infection of these viruses was extremely rare. These results show that myxoviruses such as mumps and parainfluenza virus may have a strong affinity to ependymal cells, and then they cause resultant ependymal destruction. Therefore, when the placenta is impaired so severely that these viruses are able to pass through the placental barrier, maternal infection would cause the hydrocephalus to the infant.

Animals↗

Paramyxovirus fusion (F) protein and hemagglutinin-neuraminidase (HN) protein interactions: intracellular retention of F and HN does not affect transport of the homotypic HN or F protein.

To investigate a possible intracellular coassociation of the paramyxovirus simian virus 5 (SV5) and human parainfluenza virus type 3 (HPIV-3) fusion (F) and hemagglutinin-neuraminidase (HN) glycoproteins in a living cell, without resorting to chemical crosslinking and antibody coimmunoprecipitation, we tagged the cytoplasmic N-terminus of SV5 HN with a RRRRR motif and HPIV-3 HN with a RRR motif for endoplasmic reticulum (ER) retention. In addition, we tagged the cytoplasmic C-terminus of SV5 and HPIV-3 F with a KK motif. The RRR- or RRRRR-tagged HN molecules were coexpressed in mammalian cells together with the homologous wt F proteins, and the KK-tagged F molecules were coexpressed with the homologous wt HN proteins, and in each case the transport of the wt F or HN molecules was investigated. The data suggest that an association of F and HN of sufficient affinity to alter the transport of the reporter molecule does not occur intracellularly in the ER or the Golgi apparatus.

Biological Transport↗

Persistent SV5 virus infection in continuous cell cultures.

A continuous line of guinea pig kidney cells (CGPK/H) and a continuous line of mouse fibroblasts (L/H) spontaneously infected with parainfluenza virus SV5 were found. These cultures showed no enhanced cell degeneration or symplast formation, nor was haemagglutinin accumulation or infectious virus demonstrated in them. However, regular reproduction of ribonucleoprotein (RNP) characteristic of parainfluenza viruses, morphologically complete virions and antigens producing antibody to SV5 virus were found in the cells. Focal haemadsorption neutralized by antiserum to SV5 virus was also demonstrated. The infection persisted in the cell populations for over 2 years (the observation period) under standard conditions of cell dispersion and subcultivation.

Animals↗

[Muscle cell structure in polymyositis].

Electron microscopic investigations of muscles from patients with chronic polymyositis demonstrated presence of cytoplasmatic, tubular structures and extracellular virus-like particles. Their size, morphology and location suggest multiplication of viruses from the group of parainfluenza viruses within the muscle cell in "infected" cultures of human fetal muscles. Beside viruses belonging to the parainfluenza group presence of viruses from the herpes group was demonstrated. The latter belong to latent viruses.

Adolescent↗

Fluorescence anisotropy of viruses treated with formaldehyde and dimethyl-sulfoxide.

The fluorescence anisotropy changes observed in A-1 (H1N1) influenza and Sendai parainfluenza viruses in aqueous suspensions when formaldehyde (0.1 to 1.0 p.c.) and dimethyl-sulfoxide (0.3 to 5.0 p.c.) were added, using both intrinsic fluorescence of viral proteins and that of the membrane fluorescent probe--DPH, showed significant differences with regard to the virus and the history of the suspensions used, allowing under rigorous standardized conditions the use of fluorescence anisotropy measurements for viral antigen and vaccine control.

Dimethyl Sulfoxide↗

Post-infantile giant cell hepatitis in an elderly female patient with systemic lupus erythematosus.

A 69-year-old Japanese female was admitted because of general fatigue. Laboratory data showed elevation of serum total bilirubin, transaminase, gamma-glutamyl transpeptidase, and creatinine levels. An immunological study revealed hypergammaglobulinemia, low titer of complement, and high titers of antinuclear antibody, anti-DNA antibody, and circulating immune complexes. Antibodies to parainfluenza virus 3 were positive. Histology of the liver disclosed numerous giant cell hepatocyte transformations with the lobular architecture being slightly distorted by portal inflammation and fibrosis. These findings led us to make a diagnosis of giant cell hepatitis associated with systemic lupus erythematosus. Prednisolone was effective in improving the anemia and the serum immunoglobulin, immune complex, and antinuclear antibody levels. The addition of cyclosporine to the initial corticosteroid therapy was also beneficial in decreasing the transaminase level and in improving liver histology. The patient died of acute pneumonitis and renal failure on the 166th day after admission. Parainfluenza virus 3 and autoimmune mechanisms were thus considered to be the causes of the giant cell hepatitis.

Aged↗

Analysis of respiratory syncytial virus F, G, and SH proteins in cell fusion.

Recombinant expression of the human respiratory syncytial virus (RSV) fusion (F) glycoprotein, receptor-binding glycoprotein (G), and small hydrophobic (SH) protein was performed to determine the role(s) of these proteins in syncytia formation. These studies used a vaccinia virus expressing the bacteriophage (T7) RNA polymerase gene and plasmid vectors containing the RSV genes under the control of a T7 promoter. Within the context of this expression system, expression of any individual RSV gene, or coexpression of F+G genes, did not elicit the formation of syncytia. However, at plasmid input levels which were 10-fold higher than those normally used, coexpression of F+G induced low but detectable levels of cell fusion. In contrast, coexpression of F, G, and SH together elicited extensive cell fusion resembling that of an authentically infected cell monolayer. In addition, coexpression of F and SH elicited significant cell fusion, although to a lesser extent than was observed when G was included. Cell fusion induced by coexpression of F+SH was found to be specific to the RSV proteins, since coexpression of SH with the analogous F proteins from human parainfluenza virus type 3, human parainfluenza virus type 2, Sendai virus, or simian virus type 5 (SV5) did not elicit cell fusion. Finally, coexpression of the SV5 SH protein with the RSV or SV5 glycoproteins also failed to induce syncytia, suggesting type-specific restrictions between the two sets of viral proteins.

Animals↗

Comparison of antibodies against different viruses in cerebrospinal fluid and serum samples from patients with multiple sclerosis.

The occurrence of a local production in the central nervous system (CNS) of antibodies against different selected viruses was analyzed by comparison of titers in serum and cerebrospinal fluid samples from groups of 50 patients with multiple sclerosis from Finland, Norway, and Sweden. Measles antibodies were determined in hemagglutination inhibition, hemolysis inhibition, and nucleocapsid complement fixation tests; mumps, parainfluenza virus type 1, and rubella virus antibodies were determined in hemagglutination inhibition tests; and herpes simplex virus type 1 antibodies were determined in passive hemagglutination tests. For reference purposes tests were also made for adenovirus antibodies in penton hemagglutination enhancement tests and poliovirus antibodies in neutralization enhancement tests. Among the 150 multiple sclerosis patients, a local production of antibodies against measles virus was found in the CNS in 57%, against rubella virus in 19%, mumps virus in 15%, herpes simplex virus type 1 in 11%, and parainfluenza virus type 1 (Sendai) in 3%. A local production in the CNS of antibodies against any of the viruses studied was found in 71% of multiple sclerosis patients. These included 48, 16, and 7% that produced antibodies to one, two, and three or more viruses, respectively.

Adenoviridae↗

Polyploid measles virus with hexameric genome length.

Particles of most virus species accurately package a single genome, but there are indications that the pleomorphic particles of parainfluenza viruses incorporate multiple genomes. We characterized a stable measles virus mutant that efficiently packages at least two genomes. The first genome is recombinant and codes for a defective attachment protein with an appended domain interfering with fusion-support function. The second has one adenosine insertion in a purine run that interrupts translation of the appended domain and restores function. In that genome, a one base deletion in a different purine run abolishes polymerase synthesis, but restores hexameric genome length, thus ensuring accurate RNA encapsidation, which is necessary for efficient replication. Thus, the two genomes are complementary. The infection kinetics of this mutant indicate that packaging of multiple genomes does not negatively affect growth. We also show that polyploid particles are produced in standard infections at no expense to infectivity. Our results illustrate how the particles of parainfluenza viruses efficiently accommodate cargoes of different volume, and suggest a mechanism by which segmented genomes may have evolved.

Animals↗

Transplacental transfer of antibodies to some respiratory viruses.

A group of 200 paired mother-newborn sera (umbilical sera) were used for the determination, by hemagglutination inhibition test of antibody levels for parainfluenza virus types 1, 2 and 3 and, by ELISA test of class IgG antibodies for Respiratory Syncytial Virus (RSV). In 54 paired sera the RSV antibodies also were determined in IgG subclasses and in 4 paired sera RSV protein antibodies were determined by Western-Blot in IgG class and IgG subclasses. Parainfluenza virus antibodies were found to occur in higher titres in the newborn than in the mother sera. On the other hand, IgG class antibodies for RSV were shown in more mothers than in their newborns. In the IgG-1 subclass RSV antibodies were more frequent among newborns than in their mothers, the reverse situation was observed in the IgG-2 and IgG-3 subclasses. In the IgG-4 subclass per cent of mothers and newborns who had antibodies was equal. In the Western-Blot assay, most bands corresponding to antibodies for RSV proteins were detected in the IgG class of mother sera, and in the IgG-1 subclass in newborn sera. Rather distinct transfer of antibodies for protein G was found in the IgG class, and a little lower--in the IgG-1 and IgG-3 subclasses.

Antibodies, Viral↗

Antigen detection in the diagnosis of viral infections.

The value of viral antigen detection from nasopharyngeal secretion (NPS) by enzyme immunoassay (EIA) in everyday clinical practice was evaluated in 570 children hospitalized because of infections. NPS-EIA gave a positive result in 32% of all cases. Virus isolation was positive in the NPS in 25%, virus isolation in stool samples in 14%, and virus serology in 28% of the cases. NPS-EIA was superior for detecting adenovirus, respiratory syncytial (RS) and parainfluenza viruses. In a series of 124 patients in whom 3 methods were compared, NPS-EIA was the only positive method in 48% of all findings positive for adenoviruses, in 73% for RSV, and in 58% for parainfluenza viruses. Antigen detection by NPS-EIA markedly increased the diagnostic potential in everyday clinical practice, especially for viral respiratory diseases.

Adenovirus Infections, Human↗