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Viruses May 2024Respiratory syncytial virus (RSV) is the most prevalent cause of acute lower respiratory infection in young children. Currently, the first RSV vaccines are approved by...
Respiratory syncytial virus (RSV) is the most prevalent cause of acute lower respiratory infection in young children. Currently, the first RSV vaccines are approved by the FDA. Recently, N6-methyladenosine (mA) RNA methylation has been implicated in the regulation of the viral life cycle and replication of many viruses, including RSV. mA methylation of RSV RNA has been demonstrated to promote replication and prevent anti-viral immune responses by the host. Whether mA is also involved in viral entry and whether mA can also affect RSV infection via different mechanisms than methylation of viral RNA is poorly understood. Here, we identify mA reader YTH domain-containing protein 1 (YTHDC1) as a novel negative regulator of RSV infection. We demonstrate that YTHDC1 abrogates RSV infection by reducing the expression of RSV entry receptor CX3C motif chemokine receptor 1 (CX3CR1) on the cell surface of lung epithelial cells. Altogether, these data reveal a novel role for mA methylation and YTHDC1 in the viral entry of RSV. These findings may contribute to the development of novel treatment options to control RSV infection.
Topics: Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Adenosine; Virus Internalization; CX3C Chemokine Receptor 1; Virus Replication; Methylation; Down-Regulation; RNA Splicing Factors; Epithelial Cells; Cell Line; A549 Cells; RNA, Viral; Host-Pathogen Interactions; Nerve Tissue Proteins
PubMed: 38793659
DOI: 10.3390/v16050778 -
Viruses May 2024Viral co-infections are frequently observed among children, but whether specific viral interactions enhance or diminish the severity of respiratory disease is still...
Viral co-infections are frequently observed among children, but whether specific viral interactions enhance or diminish the severity of respiratory disease is still controversial. This study aimed to investigate the type of viral mono- and co-infections by also evaluating viral correlations in 3525 respiratory samples from 3525 pediatric in/outpatients screened by the Allplex Respiratory Panel Assays and with a Severe Acute Respiratory Syndrome-COronaVirus 2 (SARS-CoV-2) test available. Overall, viral co-infections were detected in 37.8% of patients and were more frequently observed in specimens from children with lower respiratory tract infections compared to those with upper respiratory tract infections (47.1% vs. 36.0%, = 0.003). SARS-CoV-2 and influenza A were more commonly detected in mono-infections, whereas human bocavirus showed the highest co-infection rate (87.8% in co-infection). After analyzing viral pairings using Spearman's correlation test, it was noted that SARS-CoV-2 was negatively associated with all other respiratory viruses, whereas a markedly significant positive correlation ( < 0.001) was observed for five viral pairings (involving adenovirus/human bocavirus/human enterovirus/metapneumoviruses/rhinovirus). The correlation between co-infection and clinical outcome may be linked to the type of virus(es) involved in the co-infection rather than simple co-presence. Further studies dedicated to this important point are needed, since it has obvious implications from a diagnostic and clinical point of view.
Topics: Humans; Coinfection; Respiratory Tract Infections; Italy; Child, Preschool; Child; Infant; Female; Male; Tertiary Care Centers; COVID-19; SARS-CoV-2; Hospitals, Pediatric; Adolescent; Human bocavirus; Virus Diseases; Hospitalization; Viruses; Infant, Newborn; Metapneumovirus
PubMed: 38793631
DOI: 10.3390/v16050750 -
Viruses Apr 2024Respiratory syncytial virus (RSV) is an important cause of childhood hospitalizations. The aim of the study was to estimate the rates of RSV-related hospitalizations in... (Observational Study)
Observational Study
Epidemiology of Respiratory Syncytial Virus Hospitalizations in Poland: An Analysis from 2015 to 2023 Covering the Entire Polish Population of Children Aged under Five Years.
BACKGROUND
Respiratory syncytial virus (RSV) is an important cause of childhood hospitalizations. The aim of the study was to estimate the rates of RSV-related hospitalizations in children aged less than 5 years in Poland.
METHODS
This retrospective observational cohort study was based on data obtained from the National Health Fund in Poland regarding all acute respiratory tract infections and RSV-coded admissions of children (age < 5 years) to public hospitals between July 2015 and June 2023. Patients were stratified based on the following age groups: 0-1 month, 2-3 months, 4-6 months, 7-12 months, 13-24 months, and 25-60 months.
RESULTS
The number of RSV-related hospitalizations increased every season, both before and through the ending phase of the coronavirus disease 2019 (COVID-19) pandemic. The COVID-19 pandemic was associated with a shift in the seasonality pattern of RSV infection. Hospitalization rates per 1000 inhabitants were the highest for children aged 0-12 months, reaching 47.3 in the 2022/23 season. Within this group, the highest hospitalization rate was observed for children aged 2-3 months-94.9 in the 2022/23 season. During the ending phase of the COVID-19 pandemic, the observed increase in admission rates was 2-, 4-, and 5-fold the pre-COVID rate for children aged <12 months, 12-24 months, and 25-60 months, respectively.
CONCLUSIONS
In Poland, RSV infections cause a significant burden in hospitalized children aged less than 5 years. RSV-related hospitalizations were most frequent in children aged less than 1 year. The COVID-19 pandemic was associated with a shift in the seasonality pattern of RSV infections. After the pandemic, more RSV-related hospitalizations were observed in older children (aged 13 months and older) vs. the pre-pandemic phase.
Topics: Humans; Poland; Respiratory Syncytial Virus Infections; Hospitalization; Infant; Child, Preschool; Retrospective Studies; Female; Male; Infant, Newborn; COVID-19; Seasons; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; SARS-CoV-2
PubMed: 38793586
DOI: 10.3390/v16050704 -
Viruses Apr 2024Acute respiratory infections are a major global burden in resource-limited countries, including countries in Africa. Although COVID-19 has been well studied since the...
Acute respiratory infections are a major global burden in resource-limited countries, including countries in Africa. Although COVID-19 has been well studied since the pandemic emerged in Gabon, Central Africa, less attention has been paid to other respiratory viral diseases, and very little data are available. Herein, we provide the first data on the genetic diversity and detection of 18 major respiratory viruses in Gabon during the COVID-19 pandemic. Of 582 nasopharyngeal swab specimens collected from March 2020 to July 2021, which were SARS-CoV-2 negative, 156 were positive (26%) for the following viruses: enterovirus (20.3%), human rhinovirus (HRV) (4.6%), human coronavirus OC43 (1.2%), human adenovirus (0.9%), human metapneumovirus (hMPV) (0.5%), influenza A virus (IAV) (0.3%), and human parainfluenza viruses (0.5%). To determine the genetic diversity and transmission route of the viruses, phylogenetic analyses were performed using genome sequences of the detected viruses. The IAV strain detected in this study was genetically similar to strains isolated in the USA, whereas the hMPV strain belonging to the A2b subtype formed a cluster with Kenyan strains. This study provides the first complete genomic sequences of HRV, IAV, and hMPV detected in Gabon, and provides insight into the circulation of respiratory viruses in the country.
Topics: Humans; Gabon; Genetic Variation; Phylogeny; COVID-19; Respiratory Tract Infections; SARS-CoV-2; Male; Adult; Female; Child; Middle Aged; Adolescent; Child, Preschool; Young Adult; Rhinovirus; Viruses; Metapneumovirus; Genome, Viral; Nasopharynx; Infant; Aged; Pandemics; Influenza A virus
PubMed: 38793579
DOI: 10.3390/v16050698 -
Viruses Apr 2024The incidence of respiratory syncytial virus (RSV) in adults is inadequately defined and the impact of SARS-CoV-2-related non-pharmaceutical interventions (NPIs) is...
The incidence of respiratory syncytial virus (RSV) in adults is inadequately defined and the impact of SARS-CoV-2-related non-pharmaceutical interventions (NPIs) is underexplored. Using laboratory data, we described the detection rate of RSV in adults ≥16 years in Western Australia (WA) between 2017 and 2023. With the exception of 2020, RSV detections rose annually between 2017 and 2023, reaching 50.7 per 100,000 in 2023 (95% confidence interval [CI], 47.9-53.8). RSV testing expanded considerably across the study period, with the testing in 2023 more than five times the 2017 total. The detection rate was highest in adults ≥60 years between 2017 and 2019, particularly those ≥75 years. Following 2020, the detections in all age groups increased, with the highest detection rate in 2023 in those ≥75-years (199.5 per 100,000; 95% CI, 180.5-220). NPIs significantly impacted RSV seasonality; the preceding winter pattern was disrupted, resulting in an absent 2020 winter season and two major summer seasons in 2020/21 and 2021/22. The RSV season began to realign in 2022, reverting to a winter seasonal pattern in 2023 and the largest season in the study period. Ongoing surveillance will be required to understand the stability of these increases and to delineate the impact of new immunisation strategies.
Topics: Humans; Respiratory Syncytial Virus Infections; Adult; Western Australia; Middle Aged; Aged; Young Adult; Adolescent; Seasons; Respiratory Syncytial Virus, Human; Female; COVID-19; Male; Incidence; SARS-CoV-2; Aged, 80 and over
PubMed: 38793538
DOI: 10.3390/v16050656 -
[Preparation of a mouse monoclonal antibody against the NS1 protein of respiratory syncytial virus].Sheng Wu Gong Cheng Xue Bao = Chinese... May 2024The aim of this study was to prepare a mouse monoclonal antibody against the nonstructural protein 1 (NS1) of respiratory syncytial virus (RSV) to analyze its expression...
The aim of this study was to prepare a mouse monoclonal antibody against the nonstructural protein 1 (NS1) of respiratory syncytial virus (RSV) to analyze its expression and distribution during transfection and infection. Additionally, we aimed to evaluate the antibody's application in immunoprecipitation assay. Firstly, the NS1 gene fragment was cloned into a prokaryotic plasmid and expressed in . The resulting NS1 protein was then purified by affinity chromatography, and used to immunize the BALB/c mice. Subsequently, hybridoma cells capable of stably secreting the NS1 monoclonal antibody were selected using indirect enzyme linked immunosorbent assay (ELISA). This monoclonal antibody was employed in both indirect immunofluorescence assay (IFA) and Western blotting to analyze the expression and distribution of RSV NS1 in overexpressed and infected cells. Finally, the reliability of this monoclonal antibody was evaluated through the immunoprecipitation assay. The results showed that the RSV NS1 protein was successfully expressed and purified. Following immunization of mice with this protein, we obtained a highly specific RSV NS1 monoclonal antibody, which belonged to the IgG1 subtype with an antibody titer of 1:15 360 000. Using this monoclonal antibody, the RSV NS1 protein was identified in both transfected and infected cells. The IFA results revealed predominant distribution of NS1 in the cytoplasm and nucleus. Moreover, we confirmed that this monoclonal antibody could effectively bind specifically to NS1 protein in cell lysates, making it suitable as a capture antibody in immunoprecipitation assay. In conclusion, our study successfully achieved production of the RSV NS1 protein through a prokaryotic expression system and prepared a specific monoclonal antibody against NS1. This antibody demonstrates the ability to specifically identify the NS1 protein and can be used in the immunoprecipitation assay, thereby laying a foundation for the functional studies of the NS1 protein.
Topics: Animals; Female; Mice; Antibodies, Monoclonal; Antibodies, Viral; Escherichia coli; Hybridomas; Mice, Inbred BALB C; Respiratory Syncytial Viruses; Viral Nonstructural Proteins
PubMed: 38783814
DOI: 10.13345/j.cjb.230736 -
Human Vaccines & Immunotherapeutics Dec 2024This study assessed three Ad26.RSV.preF/RSV preF protein combinations, combining different Ad26.RSV.preF doses and naturally aged preF protein, representing the expected... (Randomized Controlled Trial)
Randomized Controlled Trial
This study assessed three Ad26.RSV.preF/RSV preF protein combinations, combining different Ad26.RSV.preF doses and naturally aged preF protein, representing the expected critical vaccine quality attributes close to release, around intermediate shelf-life (ISL) and near-presumed end-of-shelf-life (EoSL), as a way to evaluate the vaccine immunogenicity and safety throughout its shelf-life. A single dose of Ad26.RSV.preF/RSV preF protein vaccine was administered to adults 60-75 years of age. Solicited adverse events (AEs), unsolicited AEs, and serious AEs (SAEs) were assessed for 7-day, 28-day, and 6-month periods after vaccination, respectively. RSV preF-binding antibody concentrations and RSV neutralizing titers were measured 14 days post-vaccination as primary and secondary endpoints, respectively; binding antibodies were also measured 6 months post-vaccination. The RSV preF-binding antibody responses induced by Ad26.RSV.preF/RSV preF protein vaccine lots representing the critical quality attributes around ISL and near presumed EoSL were noninferior to the responses induced by the vaccine lot representing the critical quality attributes near release. The RSV preF-binding and RSV neutralizing antibody levels measured 14 days post-vaccination were similar across the 3 groups. RSV preF-binding antibody concentrations were also similar 6 months post-vaccination. Solicited AEs were mostly mild to moderate in intensity, and a decreased reactogenicity was observed from the Release group to the ISL and EoSL group. None of the reported SAEs were considered related to study vaccination. The study provided evidence of sustained immunogenicity and safety over the intended shelf-life of the Ad26.RSV.pref/RSV preF protein vaccine. The three vaccine lots had acceptable safety profiles.
Topics: Aged; Female; Humans; Male; Middle Aged; Antibodies, Neutralizing; Antibodies, Viral; Drug Stability; Drug Storage; Drug-Related Side Effects and Adverse Reactions; Immunogenicity, Vaccine; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Vaccine Potency; Double-Blind Method
PubMed: 38783590
DOI: 10.1080/21645515.2024.2344970 -
Scientific Reports May 2024Our previous findings indicated that many respiratory syncytial virus (RSV) isolates are unstable at 4 °C compared to 20 °C. Some of the strains completely lose...
Our previous findings indicated that many respiratory syncytial virus (RSV) isolates are unstable at 4 °C compared to 20 °C. Some of the strains completely lose infectivity after 24 h at 4 °C. This study analyzed the inactivation process at 4 °C using a representative strain, RSV/Sendai/851/13. After 24 h of storage at 4 °C, the virus was completely inactivated but retained its ability to attach to and to be taken into host cells. It suggested a reduced fusion ability between the viral and cellular membranes. During storage at 4 °C, the RSV fusion (F) protein underwent a conformational change and was no longer recognized by pre-fusion form-specific antibodies. When the RSV/Sendai/851/13 strain was passaged at 4 °C, a variant with an amino acid substitution, I148T, in the F protein fusion peptide was selected. Also, an amino acid change in G protein demonstrating stability at low temperatures was obtained. These results show that the inactivation of RSV at 4 °C is due to the loss of membrane fusion activity in the F protein, which cannot maintain its pre-fusion state at 4 °C.
Topics: Viral Fusion Proteins; Humans; Cold Temperature; Virus Inactivation; Respiratory Syncytial Virus, Human; Animals; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 38783052
DOI: 10.1038/s41598-024-62658-z -
BMC Infectious Diseases May 2024Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections in children worldwide. The highest incidence of severe disease is in the...
BACKGROUND
Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections in children worldwide. The highest incidence of severe disease is in the first 6 months of life, with infants born preterm at greatest risk for severe RSV infections. The licensure of new RSV therapeutics (a long-acting monoclonal antibody and a maternal vaccine) in Europe, USA, UK and most recently in Australia, has driven the need for strategic decision making on the implementation of RSV immunisation programs. Data driven approaches, considering the local RSV epidemiology, are critical to advise on the optimal use of these therapeutics for effective RSV control.
METHODS
We developed a dynamic compartmental model of RSV transmission fitted to individually-linked population-based laboratory, perinatal and hospitalisation data for 2000-2012 from metropolitan Western Australia (WA), stratified by age and prior exposure. We account for the differential risk of RSV-hospitalisation in full-term and preterm infants (defined as < 37 weeks gestation). We formulated a function relating age, RSV exposure history, and preterm status to the risk of RSV-hospitalisation given infection.
RESULTS
The age-to-risk function shows that risk of hospitalisation, given RSV infection, declines quickly in the first 12 months of life for all infants and is 2.6 times higher in preterm compared with term infants. The hospitalisation risk, given infection, declines to < 10% of the risk at birth by age 7 months for term infants and by 9 months for preterm infants.
CONCLUSIONS
The dynamic model, using the age-to-risk function, characterises RSV epidemiology for metropolitan WA and can now be extended to predict the impact of prevention measures. The stratification of the model by preterm status will enable the comparative assessment of potential strategies in the extended model that target this RSV risk group relative to all-population approaches. Furthermore, the age-to-risk function developed in this work has wider relevance to the epidemiological characterisation of RSV.
Topics: Humans; Respiratory Syncytial Virus Infections; Hospitalization; Infant; Infant, Premature; Infant, Newborn; Western Australia; Female; Respiratory Syncytial Virus, Human; Age Factors; Male; Risk Assessment; Risk Factors
PubMed: 38773455
DOI: 10.1186/s12879-024-09400-2 -
Antiviral Research Jul 2024Respiratory syncytial virus (RSV) can cause pulmonary complications in infants, elderly and immunocompromised patients. While two vaccines and two prophylactic...
Respiratory syncytial virus (RSV) can cause pulmonary complications in infants, elderly and immunocompromised patients. While two vaccines and two prophylactic monoclonal antibodies are now available, treatment options are still needed. JNJ-7184 is a non-nucleoside inhibitor of the RSV-Large (L) polymerase, displaying potent inhibition of both RSV-A and -B strains. Resistance selection and hydrogen-deuterium exchange experiments suggest JNJ-7184 binds RSV-L in the connector domain. JNJ-7184 prevents RSV replication and transcription by inhibiting initiation or early elongation. JNJ-7184 is effective in air-liquid interface cultures and therapeutically in neonatal lambs, acting to drastically reverse the appearance of lung pathology.
Topics: Antiviral Agents; Respiratory Syncytial Virus Infections; Animals; Humans; Virus Replication; Respiratory Syncytial Virus, Human; Sheep; Drug Resistance, Viral; Viral Proteins; Lung
PubMed: 38772503
DOI: 10.1016/j.antiviral.2024.105907