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[Preliminary note on the circulation of some human respiratory viruses by wild birds].

With a view to detecting infections and carriage of human respiratory viruses in wild birds, 349 serum samples collected from 21 bird species -- sedentary ones and birds with large or limited migration areas -- were investigated. The following antigens were used: influenza virus A/Hong Kong 1/68 (H3N2)), A2 England 42/73 (H3N2), A2 Victoria 3/75 (H3N2), A/New Jersey 8/76 (HswN1), B/Hong Kong 5/72; parainfluenza virus type I Sendai and type II, coronavirus OC/43. An elevated incidence of antibodies to A2 Victoria 3/75 (H3N2) and parainfluenza type I virus was detected in herons (Ardea cinerea, Nyctycorax myctycorax). The high incidence of antibodies to B/Hong Kong 5/72 (30.7% of the samples exhibited significant titers) found in the crow (Corvus corone sardonius) is ascribed to the fact that this bird is carnivorus, feeding on corpses of mammals.

Animals↗

Myxoviruses.

Myxoviruses can be divided into 2 groups, orthomyxoviruses and paramyxoviruses. the former comprise the influenza group which is subdivided into types A,B and C. Influenza B and C are purely human pathogens but influenza A, which includes a large number of antigenic subtypes, occurs in nature in pigs, horses, birds and man. All influenza A viruses irrespective of origin are chemically, biologically and genetically related. The epidemics which they cause are curious and puzzling and are an important cause of morbidity. Paramyxoviruses consist of human and animal parainfluenza viruses. The former comprise parainfluenza types 1,2,3 and 4 and mumps viruses, and, rather less certainly, measles and respiratory syncytial virus. The main animal paramyxoviruses are parainfluenza 3 (agent of shipping fever) in cattle; NDV (cause of fowl pest) and Yucaipavirus in birds; Sendai and PVM in mice; Nariva virus in rodents; possibly bovinerespiratory syncytial virus; and SV5 and SV41 in monkeys. The viruses and their place in nature will be reviewed.

Animals↗

The impact of infection with human metapneumovirus and other respiratory viruses in young infants and children at high risk for severe pulmonary disease.

We conducted a prospective, observational study to characterize the clinical manifestations of respiratory infections caused by human metapneumovirus (hMPV) and other viruses in 194 premature infants and young children with chronic lung disease or congenital heart disease in Buenos Aires. Children had 567 episodes of respiratory illness and were monitored until they were 2 years old or until the completion of the study. hMPV elicited 12 infections (2%) year-round; 30% were of moderate or greater severity. Human parainfluenza virus type 3 caused 24 infections (4%), and 5 (25%) of 20 lung infections led to hospitalization. Respiratory syncytial virus (RSV) caused 33 episodes--17% of infections and 32% of hospitalizations during the respiratory season. None of the 10 children infected with influenza virus had severe disease. The present study of at-risk children suggests that hMPV and influenza virus are infrequent agents of severe disease and highlights the need for preventive interventions against RSV in developing countries.

Adult↗

Inadequate antibody response against respiratory viral infection in long-surviving rat lung allografts.

Lung transplant recipients suffer from a high number of viral infections. It has been suggested that the defense against viral infections is impaired in lung transplants. Therefore, we investigated in rat lung transplants whether antibody responses against an intrapulmonary viral infection were impaired in 3 groups of rats with: (1) BN-to-LEW allogeneic lung transplants, (2) LEW-to-LEW syngeneic lung transplants, and (3) nontransplanted LEW lungs. All rats (including those with nontransplanted, normal lungs) were treated with cyclosporine on days 2 and 3 after operation; this treatment is adequate to induce permanent graft acceptance of the allografts. Six months after transplantation, viral infections with Sendai virus (parainfluenza type I) were induced intratracheally. At day 0, immediately before infection, and at days 4, 7, 21, and 56 after infection, 4 rats in each group were killed for histological evaluation of the lungs. The number of antibody-positive cells in the bronchus-associated lymphoid tissue (BALT) in the lungs and in the spleen, and presence of the virus in the lungs were determined by immunohistology. Serum antibody titers were followed for 56 days after infection. The allogeneically transplanted lungs failed to respond adequately against the virus: the number of antibody-positive cells in the BALT did not increase after infection, serum antibody titers were hardly detectable, and virus was present in the airways of the lungs up to day 21 after infection. In contrast, in the syngeneically and nontransplanted lungs, the number of antibody-forming cells in the BALT increased steeply until day 7, serum antibody titers rose until day 14, and virus could be detected only on day 4 after infection. This study shows that in rat lung allografts, both the local antibody production in the BALT and the systemic antibody response against a respiratory viral infection are inadequate. As a consequence, the virus is present longer in these allografted lungs and can exert its damaging effect over a longer period of time. These results may explain why lung transplants are so susceptible to viral infections.

Animals↗

Paramyxoviruses SV5 and HPIV2 assemble STAT protein ubiquitin ligase complexes from cellular components.

Signal transducer and activator of transcription (STAT) proteins are normally long-lived, but infection with certain Paramyxoviruses results in efficient loss of IFN-responsive STAT1 or STAT2. Expression of a virus-encoded protein called "V" is sufficient to mediate the destruction of STAT proteins. STAT degradation is blocked by proteasome inhibitors, strongly implicating the ubiquitin (Ub)-proteasome targeting system. We demonstrate that cellular expression of V proteins from simian virus 5 (SV5) and type II human parainfluenza virus (HPIV2) induces polyubiquitylation of STAT1 and STAT2 targets. In vitro, the V proteins catalyze Ub transfer in an ATP-dependent process that requires both Ub-activating (E1) and Ub-conjugating (E2) activities. Furthermore, SV5 and HPIV2 V-interacting protein partners were isolated by affinity purification from human cells and reveal a complex of associated cellular proteins. This complex includes both STAT1 and STAT2, and the damaged DNA binding protein, DDB1. In addition, a protein related to a family of cellular Ub ligase complex subunits, cullin 4A (Cul4A), associated with the V proteins. The roles of both DDB1 and Cul4A in STAT1 degradation by SV5 infection were analyzed using small interfering RNAs. These findings demonstrate the assembly of a V-dependent degradation complex that includes STAT1, STAT2, DDB1, and Cul4A. In agreement with prior nomenclature on SCF-type cellular E3 enzymes, we refer to this complex as VDC.

Antigen-Antibody Complex↗

Prevalence of viral respiratory tract infections in children with asthma.

BACKGROUND: Previous studies support a strong association between viral respiratory tract infections and asthma exacerbations. The effect of newly discovered viruses on asthma control is less well defined. OBJECTIVE: We sought to determine the contribution of respiratory viruses to asthma exacerbations in children with a panel of PCR assays for common and newly discovered respiratory viruses. METHODS: Respiratory specimens from children aged 2 to 17 years with asthma exacerbations (case patients, n = 65) and with well-controlled asthma (control subjects, n = 77), frequency matched by age and season of enrollment, were tested for rhinoviruses, enteroviruses, respiratory syncytial virus, human metapneumovirus, coronaviruses 229E and OC43, parainfluenza viruses 1 to 3, influenza viruses, adenoviruses, and human bocavirus. RESULTS: Infection with respiratory viruses was associated with asthma exacerbations (63.1% in case patients vs 23.4% in control subjects; odds ratio, 5.6; 95% CI, 2.7- 11.6). Rhinovirus was by far the most prevalent virus (60% among case patients vs 18.2% among control subjects) and the only virus significantly associated with exacerbations (odds ratio, 6.8; 95% CI, 3.2-14.5). However, in children without clinically manifested viral respiratory tract illness, the prevalence of rhinovirus infection was similar in case patients (29.2%) versus control subjects (23.4%, P > .05). Other viruses detected included human metapneumovirus (4.6% in patients with acute asthma vs 2.6% in control subjects), enteroviruses (4.6% vs 0%), coronavirus 229E (0% vs 1.3%), and respiratory syncytial virus (1.5% vs 0%). CONCLUSION: Symptomatic rhinovirus infections are an important contributor to asthma exacerbations in children. CLINICAL IMPLICATIONS: These results support the need for therapies effective against rhinovirus as a means to decrease asthma exacerbations.

Adolescent↗

Human Coronavirus-NL63 infections in Korean children, 2004-2006.

BACKGROUND: Human coronavirus-NL63 (HCoV-NL63) has been isolated from children with respiratory tract infections and its prevalence in Korea has not been reported. OBJECTIVES: This study was designed to investigate the presence and the clinical features of HCoV-NL63 during two winter seasons. STUDY DESIGN: During April 2004-April 2006, nasopharyngeal specimens from children hospitalized with acute respiratory disease were tested for common respiratory viruses, including RSV, influenza A, influenza B, parainfluenza viruses, and adenovirus by IFA. hMPV infection was excluded by nested RT-PCR using primers for F-gene. To detect HCoV-NL63, previously described nested PCR assays for 1a and 1b were used. PCR products of the 1a gene for HCoV-NL63 were sequenced. RESULTS: Out of 872 nasopharyngeal aspirate from children aged under 16 years, 14 (1.7%) were positive for HCoV-NL63. Most of the patients had croup (64.2%) or bronchiolitis (21.4%). The peak prevalence was found in November (28.5%). Most were collected between November 2004 and February 2005. CONCLUSIONS: HCoV-NL63 may be one of the causative agents of acute respiratory tract infection, especially croup.

Acute Disease↗

Growth characteristics of canine pathogenic viruses in MDCK cells cultured in RPMI 1640 medium without animal protein.

Madin Darby canine kidney (MDCK) cells were adapted to serum-free RPMI 1640 medium and used for cultivation of canine viruses. RPMI 1640 medium was supplemented with a soybean peptone, L-glutamine and antibiotics, so that the protein concentration was less than 5 microg/ml (RPMI/SP medium). The resulting adapted MDCK-SP cells showed steady growth after the twenty-eighth passage in RPMI/SP medium (MDCK-SP cell culture). Canine distemper virus, canine parvovirus, canine adenoviruses and canine parainfluenza virus, which are the principal components of canine combined virus vaccines, grew in the MDCK-SP cell culture as efficiently as the parental MDCK cells cultured in the conventional Eagle's MEM containing fetal bovine serum. Consequently, the use of MDCK-SP cell culture can make current canine vaccine products much safer, of higher quality and at lower cost.

Adenoviruses, Canine↗

Effect of heparin on a haemagglutinin of porcine reproductive and respiratory syndrome virus.

Heparin inhibited haemagglutination by porcine reproductive and respiratory syndrome virus (PRRSV) and by Aujesky's disease virus, but failed to inhibit haemagglutination by parainfluenza virus type 3. The minimal inhibitory concentration of heparin required to inhibit 8 HA U of PRRSV haemagglutinin ranged from 0.1 to 1 U ml-1. Mouse erythrocytes failed to combine with the haemagglutination inhibitory factor of heparin. However, mouse erythrocytes treated with heparinase had greatly reduced agglutinability by PRRSV. The formation of a haemagglutinin-heparin complex could be observed by sedimenting heparin with the haemagglutinin. All these findings suggest that a heparin-like molecule on the surface of mouse erythrocytes serves as the virus-cell receptor.

Animals↗

Is giant cell arteritis an infectious disease? Biological and epidemiological evidence.

The etiology of giant cell arteritis and polymyalgia rheumatica remains unknown, although the HLA-DR4 group and the pre-existence of a degenerative vascular disease are confirmed risk factors. The incidence may vary between countries, but the North-South gradient should be considered with caution because of potential detection and collection bias. Infectious trigger factors have been looked for both at the epidemiological and biological level: annual, cyclic variations of incidence have been shown in Minnesota, seasonal variations in Scotland, France or Israel. The pre-existence of clinical, mainly respiratory, infection has been suggested in one study, but not confirmed afterwards. Simultaneous occurrence of peaks of GCA/PMR and respiratory infections have been observed in Denmark. Several viruses have been suspected as triggers and assessed by serological testing, PCR or immunostaining on temporal artery biopsies, or both techniques: the hepatitis B virus can be ruled out, as well as Herpes simplex 1 and 2, Herpes varicellae, Epstein-Barr virus and cytomegalovirus. Recent studies focused on parainfluenza virus, Parvovirus B19 and Chlamydia pneumoniae. Immunological studies suggest, at the origin of the inflammatory reaction leading to the typical pathological features of giant cell arteritis, the existence of a triggering antigen of unknown nature activating T-cells in the artery wall.

Chlamydophila pneumoniae↗

Antibody testing against canine coronavirus by immunoperoxidase plaque staining.

The application of the immunoperoxidase (IP) plaque staining procedure (IP test) to the diagnosis of canine coronavirus (CCV) infection was investigated. The IP test did not react with sera from either 15 specific pathogen-free (SPF) dogs or 7 SPF dogs immunized with a multivalent vaccine, including canine parvovirus type 2, canine distemper virus, canine adenovirus type 2, and canine parainfluenza virus. To compare the IP test with the neutralizing test (NT), sera from 240 healthy dogs and from 3 experimentally CCV-infected dogs were examined. All 60 sera positive for NT antibody were positive for IP antibody, and all 180 sera negative for NT antibody were negative for IP antibody in the healthy dogs. The IP titres showed similar changes with time after CCV inoculation to those of the NT titres in the experimentally infected dogs. These findings indicate that the IP test specifically detected anti-CCV antibodies. When the IP test and NT were compared in dogs with diarrhoeic signs. 2.1% of 48 sera and 20.3% of 74 sera, which were all negative for NT antibody, were positive for IP antibody in the dogs of under one year of age and at least one year of age, respectively. The difference between the IP and NT titres (log10 [reciprocal of IP titre] log10 [reciprocal of NT titre]) for the diarrhoeic dogs of under one year of age (2.350 +/- 0.931) was significantly larger than that for the healthy dogs (0.982 +/- 0.447) (p<0.0001), the NT titre being negative or very low, despite a high IP titre in many diarrhoeic dogs. Hence, the IP test is more able to detect anti-CCV antibodies, especially in dogs showing clinical signs. The IP-positivity rate was significantly higher in the diarrhoeic dogs of under one year of age (48.7%) than in the healthy dogs (25.0%) (chi2 = 19.844, p<0.0001), suggesting that CCV may contribute to diarrhoea in many juvenile dogs.

Animals↗

Human metapneumovirus-associated lower respiratory tract infections among hospitalized human immunodeficiency virus type 1 (HIV-1)-infected and HIV-1-uninfected African infants.

Respiratory tract infections due to human metapneumovirus (hMPV) have been reported worldwide, with the exception of Africa. The prevalence of hMPV infection was studied among human immunodeficiency virus type 1 (HIV-1)-infected and HIV-1-uninfected African infants who were hospitalized for lower respiratory tract infections (LRTIs). Nasopharyngeal aspirate samples obtained from 81 HIV-1-infected and 110 HIV-1-uninfected infants who had tested negative for other respiratory viruses were selected for investigation. hMPV was detected in 10 HIV-1-uninfected infants (9.1%) and 3 HIV-1-infected infants (3.7%). Compared with the entire cohort of HIV-1-uninfected infants, hMPV was 4.6-fold less common than respiratory syncytial virus, but it was 3.2-fold more common than influenza virus and 2.1-fold more common than parainfluenza virus types 1-3. Genotyping of 7 of 14 isolates revealed the circulation of 2 major phylogenetic groups of the virus, which were similar to those described in North America and Europe.

Africa↗

The sudden infant death syndrome and epidemic viral disease.

A study was done to investigate the relationship between the sudden infant death syndrome (SIDS) and epidemic respiratory viral disease among hospitalized children under 18 months of age. During the 42 month-period of this study, there were 778 sudden infant deaths in Chicago and 3244 hospital admissions of children under 18 months for respiratory disease. Four outbreaks of respiratory syncytial (RS) virus infections, three outbreaks of influenza A virus infections, and several small clusters of parainfluenza virus infections occurred during the course of this study. Influenza A was the only virus infection found to have a statistically significant association with SIDS. Although environmental temperature was also significantly correlated with SIDS, the association with influenza A virus infection was independent of this temperature effect and neither association was strong.

Black People↗

Respiratory virus infections in children with cancer or HIV infection.

Most studies focusing on respiratory infections in immunocompromised children have been addressed to bacterial etiology. However, respiratory virus infections in this population can also lead to severe disease. The objective of this study is to evaluate the clinical significance of respiratory virus infections in children with cancer or human immunodeficiency virus (HIV) infection. Retrospective study conducted in a teaching hospital in Madrid. Medical records from children <or=14 years diagnosed with cancer or with HIV infection were reviewed. We analyzed demographic characteristics, clinical syndromes associated with the infection, need for hospitalization, treatment prescribed, and outcome. Fifty-three respiratory viral infections were identified: 26 (20%) in 129 HIV-infected children and 27 (12%) in 218 children with cancer. Twenty (38%) of the respiratory infections were nosocomial. Causal viruses were: respiratory syncytial virus, 43%; influenza A, 26%; adenovirus, 13%; parainfluenza virus, 13%; and influenza B, 4%. Thirty-three children were hospitalized: 14 (54%) with HIV infection and 19 (70%) receiving anticancer chemotherapy. Pneumonia occurred in 11 (34%) of the 33 hospitalized children. Four (21%) of the 19 hospitalized children with cancer, but none of the HIV-infected children, were admitted to the Pediatric Intensive Care Unit (P=0.096). Two children with cancer died. Common respiratory virus infections in children with cancer or HIV infection have a relevant morbidity. The fact that 40% of these infections are hospital-acquired emphasizes the need for isolation and preventive measures.

Adolescent↗

Characterization of human metapneumovirus infections in Israel.

Respiratory tract infections are a leading cause of morbidity and mortality worldwide. Even with the advancement of diagnostic tools, the causative agent of 20 to 30% of upper respiratory tract infections go undiagnosed. Recently, a newly identified human respiratory virus, human metapneumovirus (hMPV), was discovered in young children in The Netherlands. To study the prevalence of hMPV infections in Israeli children, respiratory specimens from 388 hospitalized children less than 5 years of age were evaluated for the presence of hMPV RNA, which was present in 42 (10.8%) of these samples. All hMPV-positive samples were negative for respiratory syncytial virus (RSV), influenza viruses (Flu) A and B, adenovirus, and parainfluenza viruses 1, 2, and 3. Conversely, hMPV RNA was not detected in 76 RSV-positive and 38 Flu A- or B-positive samples. Most hMPV activity was between the months February and April. Sequence analysis of 20 positive samples revealed that both of the hMPV genotypes (groups 1 and 2) have circulated in central Israel during the study period. Moreover, three of the four known hMPV subgroups (1A, 1B, and 2B) were detected among the tested samples. Seroprevalence of hMPV in 204 patients from the central part of Israel revealed that 100% of the children are hMPV seropositive by the age of 5 years old. We conclude that hMPV is a common respiratory pathogen in Israel, while mixed infections of hMPV with RSV or Flu in hospitalized children are apparently rare.

Adolescent↗

Proteolytic cleavage of subunits of the nucleocapsid of the paramyxovirus simian virus 5.

The protein subunits of the nucleocapsid of the parainfluenza virus simian virus 5 isolated from infected cells after dispersion with trypsin, chymotrypsin, or ficin are cleaved proteolytically. The molecular weights of the subunits which result from cleavage depend on the enzyme used, but are around 43,000, compared to the native subunit of 61,000. In most instances cleavage of the subunit appears to be due to the protease used to disperse the cell, and follows cell disruption. Nucleocapsids composed of native, uncleaved subunits can frequently be obtained from infected cells dispersed without a proteolytic enzyme; however, cleavage occasionally occurs even under those conditions, indicating that cellular proteases can at times cleave this protein. Nucleocapsids containing uncleaved subunits can be isolated from cells persistently infected with simian virus 5, indicating that persistent infection is not invariably associated with intracellular cleavage of this protein. Nucleocapsids composed of native subunits are hydrophobic, whereas those composed of the cleaved subunit can be dispersed in aqueous solution. It is suggested that the portion of the molecule removed by cleavage may be responsible for a specific interaction during virus assembly between the nucleocapsid and those areas of plasma membrane which contain the non-glycosylated viral membrane protein, which is also hydrophobic. An amino acid analysis of native and cleaved subunits has been done. The portion of the subunit removed by cleavage does not have a high proportion of hydrophobic residues, suggesting that those present are arranged together to form a hydrophobic domain. The N termini of both the native and cleaved subunits are blocked. This suggests that the portion of the molecule which is externally disposed and removed by cleavage contains the C terminus, and the cleaved subunit which reacts with the viral RNA contains the N terminus.

Amino Acids↗

Microbial inciters of acute asthma in urban Nigerian children.

BACKGROUND: In tropical Africa the role of microbial agents of acute respiratory infections in acute exacerbations of bronchial asthma remains largely unexplored. However, empirical antibacterial therapy is frequently initiated in moderate to severe cases of acute asthma with symptoms of acute respiratory infection. A study was set up to determine how often acute respiratory infection is associated with acute asthma, to identify the associated pathogens, and to proffer appropriate therapeutic suggestions. METHODS: Over a 16 month period, 86 episodes of acute asthma were studied for clinical and laboratory features of acute respiratory infection at the University College Hospital (UCH), Ibadan. Virological diagnosis was based on immunofluorescence studies of nasopharyngeal aspirates and/or serological tests using the microtitre complement fixation technique. Throat swabs and blood were cultured for bacterial agents. RESULTS: Of the 64 cases who presented with rhinorrhoea, 51 (79.7%) were pyrexial (T > or = 37.6 degrees C). Inflammatory changes (frequently interstitial streakiness) were identified in 10 (19.6%) of the 51 chest radiographs; only two of these had lobar shadowing. Significant bacterial isolates were made in only three (3.5%) of the throat swabs and two (2.4%) of the blood cultures from the 86 cases; none had clinical septicaemia. On the other hand, 55 viral agents were identified from 39 (53%) of the 74 subjects studied; 16 (41.0%) had dual viral identifications. Respiratory syncytial virus (RSV) accounted for 20 (36.4%) identifications, parainfluenza virus (PIV) type 3 for 15 (27.3%), and influenza type A (Flu A) for 12 (21.8%). Viral identifications were significantly higher in infants and preschool subjects (< 5 years) and in those presenting with either rhinorrhoea or pyrexia. CONCLUSIONS: The results of this study underscore the importance of viral upper respiratory infections in asthma exacerbations in a tropical setting. The paucity of clinical and investigative features of bacterial acute respiratory infection suggests that there is little rationale for routine antibiotic cover in children with acute exacerbations of asthma in the tropics.

Acute Disease↗

[Etiology of acute viral respiratory tract infections in children from Gran Canaria, the Canary Islands (Spain)].

OBJECTIVE: Acute respiratory tract infections (ARTI) of viral origin are a frequent cause of pediatric consultations and hospital admissions. The aim of this study was to investigate the etiology of these infections in Gran Canaria, the Canary Islands, (Spain). METHODS: From May 2002 through May 2005, 1957 nasopharyngeal washings were collected from 1729 children presenting with ARTI to the Pediatric Emergency Unit. A rapid antigen detection method was performed in every sample to identify respiratory syncytial virus (RSV). An immunofluorescence assay (IFA) and cell culture (CC) was used in RSV-negative samples. RESULTS: Median age was 2 months (range, 0.03-119). A viral agent was identified in 1032 children (59.7%). RSV was detected in 769 children (74.5%). Other viruses identified, in order of frequency, were parainfluenza viruses, rhinoviruses, adenoviruses, influenza viruses, enteroviruses, and coronaviruses. Statistical differences were found between age and the type of virus detected: Adenoviruses caused respiratory infections in older children (median age: 6 months; range: 1-74). There were 6 mixed infections. Sensitivity of IFA as compared to CC was 55.8%, and specificity was 99.2%. CONCLUSIONS: Respiratory viruses are responsible for a large number of ARTI cases in children from Gran Canaria, RSV being the major cause. Viral identification is determinant for managing these patients and making a proper use of antibacterial and antiviral drugs.

Acute Disease↗