Studies Of Respiratory Syncytial Virus Research Articles

Prospective hospital-based cohort studies of Respiratory Syncytial Virus (RSV) infections in infants under one year during and after the SARS-CoV-2 pandemic in Japan

ObjectivesIn Japan, population-based epidemiological data on respiratory syncytial virus (RSV) infections are limited. To elucidate the epidemiology of RSV before the introduction of new prophylactic drugs, we conducted a population-based study during and after the SARS-CoV-2 pandemic. MethodsThis study was performed in four hospitals in Chiba City and three hospitals in Ichihara City. Clinical information and residual samples from RSV rapid antigen tests of infants under one year old were collected. Samples from patients with lower respiratory tract infections (LRTI) were analyzed using the FilmArray Respiratory 2.1 panels. ResultsA total of 1200 infants underwent the RSV rapid antigen test, with 497 diagnosed with LRTI. Although five samples could not be stored, 252 out of 492 (51.2%) were positive for RSV. Among the RSV PCR-positive infants, 63 (25.0%) had underlying diseases, compared to 100 out of 240 (41.7%) RSV PCR-negative infants (P < 0.05). In Chiba City, the annual incidence of hospitalization per 1000 children was 12.7 in 2021, 4.4 in 2022, and 9.2 in 2023. ConclusionsDuring and after the SARS-CoV-2 pandemic, most hospitalized infants with RSV-LRTI did not have underlying diseases. Widespread use of prophylaxis in infants without underlying disease is desirable.

Quantifying the effect of defective viral genomes in respiratory syncytial virus infections.

Defective viral genomes (DVGs) are viral genomes that contain only a partial viral RNA and so cannot replicate within cells on their own. If a cell containing DVGs is subsequently infected with a complete viral genome, the DVG can then use the missing proteins expressed by the full genome in order to replicate itself. Since the cell is producing defective genomes, it has less resources to produce fully functional virions and thus release of complete virions is often suppressed. Here, we use data from challenge studies of respiratory syncytial virus (RSV) in healthy adults to quantify the effect of DVGs. We use a mathematical model to fit the data, finding that late onset of DVGs and prolonged DVG detection are associated with lower infection rates and higher clearance rates. This result could have implications for the use of DVGs as a therapeutic.

A molecular epidemiological study of respiratory syncytial virus circulating in southern Zhejiang Province, China, from 2009 to 2014

To find out the prevalence of respiratory syncytial virus (RSV) genotypes in southern Zhejiang Province, China, and to study the genetic characteristics of G protein from subtype A of RSV. The lower respiratory tract secretions of children under 5 years of age who were hospitalized for pneumonia and bronchiolitis in three hospitals in southern Zhejiang Province from July 2009 to June 2014 were collected. Direct immunofluorescence assay was used to detect RSV antigens from the collected secretions. A total of 200 samples were randomly selected from RSV-positive specimens in each prevailing year (from July of a specific year to June of the next year). RT-PCR was used to determine RSV subtypes, and the near-full length gene sequence of G protein from subtype A was amplified and sequenced to identify the genotype. A total of 25 449 samples of lower respiratory tract secretions were collected from 2009 to 2014, among which 6 416 (25.21%) samples were RSV-positive. Among the 1 000 RSV-positive specimens randomly sampled, 462 strains (46.2%) were subtype A, and 538 strains (53.8%) were subtype B. Subtype A accounted for 22.5%, 74.5%, 84.5%, 19.0%, and 30.5% of the total strains in each year from 2009 to 2014. A total of 25 RSV subtype A strains were randomly sampled and sent out for bidirectional sequencing in each year, which confirmed 52 positive subtype A strains. Four genotypes of subtype A strains were obtained from the above strains, including NA1 (39 strains), NA4 (1 strain), ON1 (10 strains), and GA2 (2 strains). NA1 was the dominant genotype between 2009 and 2012, and ON1 was the only genotype of subtype A during 2013-2014. The nucleotide homology and amino acid homology between the G protein of subtype A and the prototype strain A2 were 80.7%-89.3% and 74.4%-82.6%, respectively. The nucleotide homology and amino acid homology between the isolates of subtype A were 81.5%-100% and 80.2%-100%, respectively. In southern Zhejiang Province from 2009 to 2014, there was a co-circulation of RSV subtypes A and B, as well as a co-circulation of several different genotypes of RSV subtype A, which had highly variable G protein genes.

Molecular Study of Respiratory Syncytial Virus, Human Rhinovirus and Human Metapneumovirus, Detected in Children With Acute Wheezing

Background: Viruses are known to cause the majority of acute respiratory infections. A great deal of evidence indicates that the etiology of most cases of wheezing in children, like asthma or bronchiolitis, is also linked to such respiratory infections. Objectives: We assessed the prevalence of three common viruses including; Respiratory syncytial virus (RSV), human rhinovirus (HRV), and human Metapneumovirus (hMPV), in children with acute wheezing. Patients and Methods: Ninety six wheezy children, 48 males (50%) and 48 females (50%)under the age of 5 years, were enrolled in the study. All patients visited as outpatients or inpatients when referred to the Mofid Children Hospital, in Tehran, from September 2009 to March 2010. A nasopharyngeal sample was taken from each childs nostril and the three viruses were detected by a molecular polymerase chain reaction method (PCR). Results: Out of 96 patients, 63 cases (64.8%) had a positive PCR test for at least one virus. Prevalence of each virus including RSV, HRV and hMPV alone or in combination were 44 (45.8%), 13 (13.5%) and 6 (6.3%), respectively. There were no significant relationships between;age, prematurity, fever, respiratory distress and the existence of any kind of virus in the nasopharynx. Conclusions: Our study revealed that the prevalence of these three viruses in the nasopharyngeal secretions of children suffering from acute wheezing was similar to other studies. The results of this study concluded; PCR assay is a widely available and rapid method to detect the viral etiology which induces wheezing in children in Iran, and the study also provides a baseline for future studies about the clinical importance of this relationship.

The first two nucleotides of the respiratory syncytial virus antigenome RNA replication product can be selected independently of the promoter terminus

There is limited knowledge regarding how the RNA-dependent RNA polymerases of the nonsegmented negative-strand RNA viruses initiate genome replication. In a previous study of respiratory syncytial virus (RSV) RNA replication, we found evidence that the polymerase could select the 5'-ATP residue of the genome RNA independently of the 3' nucleotide of the template. To investigate if a similar mechanism is used during antigenome synthesis, a study of initiation from the RSV leader (Le) promoter was performed using an intracellular minigenome assay in which RNA replication was restricted to a single step, so that the products examined were derived only from input mutant templates. Templates in which Le nucleotides 1U, or 1U and 2G, were deleted directed efficient replication, and in both cases, the replication products were initiated at the wild-type position, at position -1 or -2 relative to the template, respectively. Sequence analysis of the RNA products showed that they contained ATP and CTP at the -1 and -2 positions, respectively, thus restoring the mini-antigenome RNA to wild-type sequence. These data indicate that the RSV polymerase is able to select the first two nucleotides of the antigenome and initiate at the correct position, even if the 3'-terminal two nucleotides of the template are missing. Substitution of positions +1 and +2 of the template reduced RNA replication and resulted in increased initiation at positions +3 and +5. Together these data suggest a model for how the RSV polymerase initiates antigenome synthesis.

A Classification Study of Respiratory Syncytial Virus (RSV) Inhibitors by Variable Selection with Random Forest

Experimental pEC50s for 216 selective respiratory syncytial virus (RSV) inhibitors are used to develop classification models as a potential screening tool for a large library of target compounds. Variable selection algorithm coupled with random forests (VS-RF) is used to extract the physicochemical features most relevant to the RSV inhibition. Based on the selected small set of descriptors, four other widely used approaches, i.e., support vector machine (SVM), Gaussian process (GP), linear discriminant analysis (LDA) and k nearest neighbors (kNN) routines are also employed and compared with the VS-RF method in terms of several of rigorous evaluation criteria. The obtained results indicate that the VS-RF model is a powerful tool for classification of RSV inhibitors, producing the highest overall accuracy of 94.34% for the external prediction set, which significantly outperforms the other four methods with the average accuracy of 80.66%. The proposed model with excellent prediction capacity from internal to external quality should be important for screening and optimization of potential RSV inhibitors prior to chemical synthesis in drug development.

Identification of internal sequences in the 3' leader region of human respiratory syncytial virus that enhance transcription and confer replication processivity.

Previous studies of respiratory syncytial virus have shown that the 44-nucleotide (nt) leader (Le) region is sufficient to initiate RNA replication, producing antigenome RNA, and that the Le and adjoining gene start (GS) signal of the first gene are sufficient to initiate transcription, producing mRNA. A cis-acting element necessary for both transcription and replication was mapped within the first 11 nt at the 3' end of Le. In the present study the remainder of the Le region was mapped to identify sequences important for transcription and replication. A series of minigenomes with mutant Le sequences was generated, and their ability to direct transcription and replication was determined by Northern blot analysis, which examined full-length antigenome and mRNA, and by primer extension analysis, which examined antigenome and mRNA initiation. With regard to transcription, nt 36 to 43, located immediately upstream of the GS signal, were found to be necessary for optimal levels of mRNA synthesis, although the GS signal in conjunction with the 3'-terminal region of Le was sufficient to direct accurate mRNA synthesis initiation. With regard to replication, the first 15 nt of Le were found to be sufficient to direct initiation of antigenome synthesis, but nt 16 to 34 were required in addition for efficient encapsidation and production of full-length antigenome. Analysis of transcripts produced from di- and tricistronic minigenomes indicated that a significant proportion of abortive replicases continue RNA synthesis to the end of the first gene and then continue in a transcription mode along the remainder of the genome.

Diagnosis coding in The Danish National Patient Registry for respiratory syncytial virus infections

This national registry-based epidemiological study aimed to evaluate the usefulness of the Danish National Patient Registry (DNPR) as a tool for epidemiological studies of respiratory syncytial virus (RSV) hospitalizations. Information on RSV diagnoses in records of hospitalizations among inpatients tested for RSV in Denmark from January 1996 to May 2003 in the DNPR was validated against the RSV test result in records from the 18 laboratories testing for RSV among hospitalized patients in Denmark. Of 16,733 RSV-positive samples representing a total of 14,898 hospitalizations in the DNPR, 68% (10,111) had been registered in the DNPR with 1 or more RSV diagnoses. Age influenced the odds ratio (OR) of being coded with a RSV diagnosis among patients with a RSV positive test, hence 73% of infants compared to 57% of patients beyond infancy had been registered in the DNPR with 1 or more RSV diagnoses. The OR of being coded with a RSV diagnosis among patients with an RSV positive test was increased over the study period and was also increased by increasing length of hospitalization and by the presence of secondary diagnoses. The OR was decreased by the presence of asthma and other chronic conditions in the patients. The OR was furthermore influenced by RSV seasonality and by hospital. Taking into account a loss of 27% of RSV hospitalizations, DNPR can be used for epidemiological studies of RSV among infants in Denmark.

Severe Respiratory Syncytial Virus Bronchiolitis

Background: The efficacy of palivizumab prophylaxis after bronchopulmonary dysplasia (BPD) has been demonstrated in a single placebo-controlled trial. Concern has emerged about the degree of efficacy of palivizumab. This study was designed to determine the efficacy of administration of palivizumab to premature infants with a gestational age ≤32 weeks, a past history of BPD and younger than 6 months of age at the start of the epidemic. Methods: Prospective observational study of respiratory syncytial virus (RSV) bronchiolitis requiring hospitalization in Burgundy (12 hospitals) from December 1 to April 30 of the next year during 3 successive epidemic seasons (1999-2000, 2000-2001 and 2001-2002). The regional perinatal database provided perinatal epidemiologic characteristics of the population as a whole and of cohorts of children at risk for severe RSV infection born between April 15 and January 31 of the following year. Palivizumab was used in the 2000-2001 and 2001-2002 periods only. Results: The 3 epidemics included respectively 377, 310 and 328 children born during April 15 to January 31 of the following year. The 3 epidemics differed significantly by the proportion of severely premature infants with BPD (3.2% versus 0.7 and 0.3%). In the cohort of severely premature infants with BPD born in 1999-2000, 2000-2001 and 2001-2002, the hospitalization rate for RSV bronchiolitis decreased significantly from 12 of 26 to 2 of 17 and 1 of 26 (46.2% versus 11.8 and 3.8%; P < 0.01). Sixteen of 17 and 23 of 26 premature infants with a gestational age ≤32 weeks and with BPD had been treated with palivizumab in the years 2000-2001 and 2001-2002. Conclusions: This study strongly supports the efficacy of prevention of RSV bronchiolitis by palivizumab in severely premature infants with BPD.

An epidemiological study of respiratory syncytial virus associated hospitalizations in Denmark.

Respiratory syncytial virus (RSV) is the most common viral pathogen that causes lower respiratory tract infections in infants. Studies have implicated severe RSV infections early in life as a risk factor for subsequent development of reactive airway disease. We are conducting a study to validate RSV-associated diagnoses in the Danish National Patient Registry, to assess whether the incidence of severe RSV infection is increasing in Denmark, to identify predisposing and protective factors for RSV-associated hospitalization in Denmark, and to examine the association of severe RSV infection with reactive airway disease. The influence of various biological, social and environmental factors on hospitalization for RSV infection will be studied through several population-based registers, including the Danish National Birth Cohort: 'Better health for mothers and children'. The RSV hospitalization cases will be compared with control individuals selected within the same population groups on a case–control or a cohort basis in order to produce estimates of age-adjusted and sex-adjusted relative risks (odds ratio and relative risk) for hospitalization associated with various risk factors. Using register linkage and unique registration of exposures collected through interviews and blood samples from the Danish National Birth Cohort, we will be able to resolve the issues referred to above in a very large sample of Danish children.

Clinical and epidemiological aspects of respiratory syncytial virus lower respiratory tract infections.

This paper has analyzed respiratory syncytial virus lower respiratory tract infections in 201 hospitalized children. In children with wheezing, erythrocyte sedimentation rate (ESR) was significantly higher in those with pneumonia than with syndroma pertussis, while the white blood cell (WBC) count was significantly lower in patients with bronchitis than in those with bronchiolitis and syndroma pertussis. Bronchodilatators were applied in 75.6% and corticosteroids in 20% of patients. Ten patients were ventilated. Fatal disease outcome was observed in one infant. Twelve consecutive-year study of respiratory syncytial virus (RSV) infections showed that 27.3% of these diseases were bronchiolitis and pneumonia.

Seroepidemiological study of respiratory syncytial virus in São Paulo state, Brazil.

Transmission of respiratory syncytial virus is thought to be highly seasonal based on reported clinical cases, although transmission resulting in mild disease in all age groups has been little studied. This has been investigated in a seroepidemiological survey using sera from São Paulo, Brazil. Seroprevalence was found to increase rapidly with age, reaching over 90% by three years of age. This is typical of viral infections, which produce life-long immunity following primary infection. One-hundred percent seropositivity was attained by five years of age and maintained throughout adulthood, whereas mean antibody titers continued to increase with age. The mean duration of maternal antibodies was estimated to be 3.3 months with antibody decay demonstrated in paired samples from infants. The results are discussed in relation to possible mechanisms generating such a profile.

Biophysical studies of respiratory syncytial virus. I. Density of respiratory syncytial virus and associated complement-fixing antigens in cesium chloride density gradient.

Coates, Helen V. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.), Ben R. Forsyth, and R. M. Chanock. Biophysical studies of respiratory syncytial virus. I. Density of respiratory syncytial virus and associated complement-fixing antigens in a cesium chloride density gradient. J. Bacteriol. 91:1263-1269. 1966.-Concentrated fluids from respiratory syncytial (RS) virus-infected tissue cultures (HEp-2 and BEK) were subjected to equilibrium sedimentation in cesium chloride. When two antigenically distinct strains of RS virus (Long and 18537) were tested, approximately 90% of the infectious virus was recovered in a sharp, symmetrical peak with a density of 1.22 to 1.24. In a similar study, unconcentrated virus had a density of 1.25 to 1.27. Two immunologically distinguishable complement-fixing antigens (antigens A and B) were detected at densities of 1.28 to 1.32 and 1.23 to 1.37. In addition, the existence of a third antigen (density of 1.22 to 1.30) was suggested. The possible origin of these antigens is discussed relative to the known properties of RS virus and the other myxoviruses.

Biophysical studies of respiratory syncytial virus. II. Identification of two soluble complement-fixing antigens of respiratory syncytial virus.

Forsyth, Ben R. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.), Helen V. Coates, and Robert M. Chanock. Biophysical studies of respiratory syncytial virus. II. Identification of two soluble complement-fixing antigens of respiratory syncytial virus. J. Bacteriol. 91:1270-1276. 1966.-Column chromatography of concentrated preparations was used to separate two antigenic components from the "soluble complement-fixing (CF) antigen" of respiratory syncytial (RS) virus. These antigens, designated antigen A and antigen B, stimulated homologous but not heterologous CF antibodies. Only antigen A stimulated the production of neutralizing antibody in guinea pigs. There was a dissociation between the CF and neutralizing antibody responses of guinea pigs immunized with antigen A. The two antigens were shown to have different molecular size, density, and sensitivity to lipolytic agents. Both antigens appeared to be components of the RS viral particle. Serological studies demonstrated that both antigens were formed during RS virus infection of children and adults.