The effect of respiratory syncytial virus (RSV) infection on the mouse faecal metabolome
Ontology highlight
ABSTRACT:
SUBMITTER: Helen Groves
PROVIDER: S-BSST267 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-05-29 | GSE232687 | GEO
Project description:Viral infection often triggers eukaryotic initiator factor 2α (eIF2α) phosphorylation, leading to global 5’-cap-dependent translation inhibition. RSV encodes messenger RNAs (mRNAs) mimicking 5’-cap structures of host mRNAs and thus inhibition of cap-dependent translation initiation would likely also reduce viral translation. We confirmed that RSV limits widespread translation initiation inhibition and unexpectedly found that the fraction of ribosomes within polysomes increases during infection, indicating higher ribosome loading on mRNAs during infection. We found that AU-rich host transcripts that are less efficiently translated under normal conditions become more efficient at recruiting ribosomes, similar to RSV transcripts. Viral transcripts are transcribed in cytoplasmic inclusion bodies, where the viral AU-rich binding protein M2-1 has been shown to bind viral transcripts and shuttle them into the cytoplasm. We further demonstrated that M2-1 is found on polysomes, and that M2-1 might deliver host AU-rich transcripts for translation.
2024-09-03 | GSE268742 | GEO
Project description:Respiratory Syncytial virus (RSV)
| PRJNA973580 | ENA
Project description:Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants. Effective treatment for RSV infection is a significant unmet medical need. While new RSV therapeutics are now in development, there are very few animal models that mimic the pathogenesis of human RSV, making it difficult to evaluate new disease interventions. Experimental infection of Holstein calves with bovine RSV (bRSV) causes a severe respiratory infection that is similar to human RSV infection, providing a relevant model for testing novel therapeutic agents. In this model, viral load is readily detected in nasal secretions by quantitative real-time PCR (qRT-PCR), and cumulative symptom scoring together with histopathology evaluations of infected tissue allow for the assessment of disease severity. The bovine RSV model was used to evaluate the antiviral activity of an RSV fusion inhibitor, GS1, which blocks virus entry by inhibiting the fusion of the viral envelope with the host cell membrane. The efficacy of GS1, a close structural analog of GS-5806 that is being developed to treat RSV infection in humans was evaluated in two randomized, blind, placebo-controlled studies in bRSV-infected calves. Intravenous administration of GS1 at 4 mg/kg of body weight/day for 7 days starting 24 h or 72 h postinoculation provided clear therapeutic benefit by reducing the viral load, disease symptom score, respiration rate, and lung pathology associated with bRSV infection. These data support the use of the bovine RSV model for evaluation of experimental therapeutics for treatment of RSV.
| S-EPMC4505261 | biostudies-other
Project description:RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid, an FDA-approved and safe urate-lowering drug that inhibits organic anion transporters (OATs) has prophylactic or therapeutic efficacy to inhibit RSV replication in three epithelial cell lines used in RSV studies, i.e., Vero E6 cells, HEp-2 cells, and in primary normal human bronchoepithelial (NHBE) cells, and in BALB/c mice. The studies showed that nanomolar concentrations of all probenecid regimens prevent RSV strain A and B replication in vitro and RSV strain A in vivo, representing a potential prophylactic and chemotherapeutic for RSV.
| S-EPMC9147281 | biostudies-literature
Project description:BackgroundRespiratory syncytial virus (RSV) is a common respiratory pathogen that can cause severe pneumonia. In vivo studies of RSV can be difficult due to variation in viral infection and disease severity in some animal models. Factors that may contribute to the variation are decreases in viral titer due to preparation and storage and method of virus administration. Nebulization is one method of RSV administration that provides even distribution of virus to all lung lobes; however, the exact quantity of the virus killed by nebulization is not defined. To test the hypothesis that sucrose enhances RSV stability and infectivity, a series of in vitro experiments were conducted with RSV strain Memphis 37 stored at varying concentrations (0%, 3%, 5%, 8%, 10%, 15%, and 20%) of sucrose as a possible cryo- and nebulization protectant. The optimal in vitro concentration was then assessed in vivo in a lamb model.MethodsPrior to titering the virus on HEp-2 cells, the various virus solutions were subjected to one freeze-thaw cycle and one nebulization cycle. Forty-eight hours after viral plating, infectious foci were detected and counted using immunofluorescent imaging. Titers were determined after freeze-thaw and after freeze-thaw followed by nebulization, then compared to the stock titers (before freezing) as well as to one another to determine the loss of infectivity. To further test this in vivo, lambs 2 to 3-days-old were infected via nebulization with RSV using inoculate containing either 20% sucrose or no sucrose followed by assessments of infection severity.ResultsNebulization of virus in 0% sucrose resulted in a 0.580 log reduction in infectivity while virus in 20% sucrose exhibited a 0.297 log reduction. In vivo studies demonstrated that 20% sucrose enhanced RSV lesions and antigen distribution.ConclusionsThe data suggests that both nebulization and freeze-thawing of RSV in the absence of sucrose cause unacceptable losses in viral infectivity and that sucrose acts as a RSV protectant in both regards.
| S-EPMC3995326 | biostudies-literature
Project description:Respiratory Syncytial Virus (RSV) is the most common cause of respiratory tract infection in infants and children and shows increasing trend among elderly people worldwide. In many developing country settings, population and household structures have gone through some significant changes in the past decades, namely fewer births, more elderly population, and smaller household size but more RSV high-risk individuals. These dynamics have been captured in a mathematical model with RSV transmission dynamics to predict the disease burden on the detailed population for future targeted interventions. The population and disease dynamics model was constructed and tested against the hospitalization data for Acute Lower Respiratory Tract Infection due to RSV in rural Thai settings between 2005 and 2011. The proportion of extended families is predicted to increase by about 10% from 2005 to 2020, especially for those with elderly population, while the classic nuclear family type (with adults and children) will decline by about 10%. For RSV, infections from extended family type (approximately 60% of all household types) have majorly contributed to the force of infection (FOI). While the model predicted the increase of FOI from the extended family by 15% from 2005 to 2020, the FOI contributed by other household types would be either stable or decrease in the same time period. RSV incidence rate is predominantly high among babies (92.2%) and has been predicted to decrease slightly over time (from 940 to 864 cases per 100,000 population by 2020), while the incidence rates among children and elderly people may remain steadily low over the same period. However, the estimated incidence rates among elderly people were twice than those in children. The model predicts that approximately 60% of FOI for RSV will come from members of the extended family type. The incidence rate of RSV among children and elderly in extended families was about 20 times lower than that in infants and the trend is steady. Targeted intervention strategies, such as health education in some specific groups and targeted vaccination, may be considered, with the focus on extended family type. Target interventions on babies can lessen the transmission to children and elderly especially when transmission within households of extended family type is high.
| S-EPMC6615606 | biostudies-literature
Project description:Respiratory syncytial virus (RSV) is the primary cause of lower respiratory tract infection during childhood and causes severe symptoms in some patients, which may cause hospitalization and death. Mechanisms for differential responses to RSV are unknown. Our objective was to develop an in vitro model of RSV infection to evaluate interindividual variation in response to RSV and identify susceptibility genes. Populations of human-derived HapMap lymphoblastoid cell lines (LCLs) were infected with RSV. Compared with controls, RSV-G mRNA expression varied from ~1- to 400-fold between LCLs. Basal expression of a number of gene transcripts, including myxovirus (influenza virus) resistance 1 (MX1), significantly correlated with RSV-G expression in HapMap LCLs. Individuals in a case-control population of RSV-infected children who were homozygous (n=94) or heterozygous (n=172) for the predicted deleterious A allele in a missense G/A SNP in MX1 had significantly greater risk for developing severe RSV disease relative to those with the major allele (n=108) (?(2)=5.305, P=0.021; OR: 1.750, 95% CI: 1.110, 2.758, P=0.021). We conclude that genetically diverse human LCLs enable identification of susceptibility genes (e.g., MX1) for RSV disease severity in children, providing insight for disease risk.
| S-EPMC3963017 | biostudies-literature
Project description:The innate immune response (IIR) involves rapid genomic expression of protective interferons (IFNs) and inflammatory cytokines triggered by intracellular viral replication. Although the transcriptional control of the innate pathway is known in substantial detail, little is understood about the complexity of alternative splicing (AS) and alternative polyadenylation (APA) of mRNAs underlying the cellular IIR. In this study, we applied single-molecule, real-time (SMRT) sequencing with mRNA quantitation using short-read mRNA sequencing to characterize changes in mRNA processing in the epithelial response to respiratory syncytial virus (RSV) replication. Mock or RSV-infected human small-airway epithelial cells (hSAECs) were profiled using SMRT sequencing and the curated transcriptome analyzed by structural and quality annotation of novel transcript isoforms (SQANTI). We identified 113,082 unique isoforms; 28,561 represented full splice matches, and 45% of genes expressed six or greater AS mRNA isoforms. Identification of differentially expressed AS isoforms was accomplished by mapping a short-read RNA sequencing expression matrix to the curated transcriptome, and 905 transcripts underwent differential polyadenylation site analysis enriched in protein secretion, translation, and mRNA degradation. We focused on 355 genes showing differential isoform utilization (DIU), indicating where a new AS isoform becomes a major fraction of mRNA isoforms expressed. In pathway and network enrichment analyses, we observed that DIU transcripts are substantially enriched in cell cycle control and IIR pathways. Interestingly, the RelA/IRF7 innate regulators showed substantial DIU where major transcripts included distinct isoforms with exon occlusion, intron inclusion, and alternative transcription start site utilization. We validated the presence of RelA and IRF7 AS isoforms as well as their induction by RSV using eight isoform-specific RT-PCR assays. These isoforms were identified in both immortalized and primary small-airway epithelial cells. We concluded that the cell cycle and IIR are differentially spliced in response to RSV. These data indicate that substantial post-transcriptional complexity regulates the antiviral response.
| S-EPMC7912025 | biostudies-literature
Project description:BackgroundThe nucleoprotein (N protein) of respiratory syncytial virus (RSV) is a candidate antigen for new RSV vaccine development. The aim of the present study was to investigate the association between maternal antibody titers against the RSV N protein at birth and the newborns' risk of developing very severe lower respiratory tract infection (VS-LRTI).MethodsIn this single-center prospective cohort study, 578 infants born during the RSV epidemic season in France were included. Among these, 36 were hospitalized for RSV VS-LRTI. A generalized linear model was used to test the occurrence of a VS-LRTI in function of sex, mode of delivery, parity of the mother, type of pregnancy, date of birth in relation to the peak of the epidemic, and antibody titer against N protein.ResultsAll cord blood samples had detectable antibodies against N protein. The mean titers were significantly lower in newborns with risk factors for RSV severe LRTI (preterm infants, birth before the peak epidemic, multiparous mother). There was no association between antibody titer against the N protein and a protection against VS-LRTI.ConclusionsFurther studies are needed to support the hypothesis that transfer of maternal antibodies against the RSV N protein can provide a significant immune protection early in infancy and that N protein candidate vaccine may be a suitable target for maternal vaccine.
| S-EPMC9835445 | biostudies-literature