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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Cotton rat lung transcriptome reveals host immune response to Respiratory Syncytial Virus infection
Seesandra V Rajagopala1,2, Harinder Singh2, Mira C Patel3
1Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Insights
Respiratory Syncytial Virus (RSV) infections cause significant infant hospitalizations. This study created the first cotton rat lung transcriptome to analyze the host immune response to RSV, identifying key gene expression changes.
Area of Science:
- Virology
- Immunology
- Genomics
- Animal Models
Background:
- Acute respiratory infections (ARI) caused by respiratory syncytial virus (RSV) are a leading cause of infant mortality globally.
- Cotton rats (Sigmodon hispidus) are the established animal model for studying RSV, but a lack of a reference genome hinders comprehensive host gene expression analysis.
- Understanding the host response to RSV is crucial for developing effective treatments and preventative strategies.
Purpose of the Study:
- To construct the first de novo lung tissue transcriptome for the cotton rat (Sigmodon hispidus).
- To profile the host immune response to RSV infection using the developed transcriptome.
- To identify host genes and transcripts involved in the cotton rat's response to RSV.
Main Methods:
- De novo transcriptome assembly from cotton rat lung tissue.
- Assignment of transcripts to 12,211 unique UniProt genes.
- Differential gene expression analysis following RSV infection, validated by quantitative real-time polymerase chain reaction (qRT-PCR).
Main Results:
- The cotton rat lung transcriptome was successfully constructed, enabling gene expression studies.
- RSV infection led to the up-regulation of host genes involved in antiviral defense and immune system processes.
- Specific transcripts were identified as unique to RSV-infected cotton rats, with some showing down-regulation in later infection stages.
Conclusions:
- The developed cotton rat lung transcriptome provides a valuable resource for genome-wide host gene expression studies in RSV research.
- RSV infection elicits a robust host immune response in cotton rats, characterized by specific gene expression patterns.
- This study lays the groundwork for deeper investigation into the molecular mechanisms of RSV pathogenesis and host-virus interactions.
Abstract:
Acute respiratory infection (ARI) with respiratory syncytial virus (RSV) is the most common cause of both hospitalizations and mortality in young infants worldwide. Repeat infections with RSV are common throughout life in both pediatric and elderly populations. Thus far, cotton rats (Sigmodon hispidus) are found to be the best animal model to study RSV infection. However, the lack of a cotton rat reference genome limits genome-wide host gene expression studies. We constructed the first lung tissue de novo transcriptome for the cotton rat. Cotton rat lung tissue transcripts were assigned to 12,211 unique UniProt genes, which were then utilized to profile the host immune response after RSV infection. Differential expression analysis showed up-regulation of host genes involved in cellular functions including defense responses to viral infection and immune system processes. A number of transcripts were downregulated during the later stage of infection. A set of transcripts unique to RSV-infected cotton rats was identified. To validate RNA-Seq data of three such transcripts (TR453762, TR529629, and TR5333), their expression was confirmed by quantitative real-time polymerase chain reaction.
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