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1. Species-specific transcriptomic changes upon respiratory syncytial virus infection in cotton rats

Author

Britton A. Strickland, Seesandra V. Rajagopala, Arash Kamali, Meghan H. Shilts, Suman B. Pakala, Marina S. Boukhvalova, Shibu Yooseph, Jorge C. G. Blanco, and Suman R. Das

Subjects
Medicine, Science
Abstract

Abstract The cotton rat (Sigmodon) is the gold standard pre-clinical small animal model for respiratory viral pathogens, especially for respiratory syncytial virus (RSV). However, without a reference genome or a published transcriptome, studies requiring gene expression analysis in cotton rats are severely limited. The aims of this study were to generate a comprehensive transcriptome from multiple tissues of two species of cotton rats that are commonly used as animal models (Sigmodon fulviventer and Sigmodon hispidus), and to compare and contrast gene expression changes and immune responses to RSV infection between the two species. Transcriptomes were assembled from lung, spleen, kidney, heart, and intestines for each species with a contig N50 > 1600. Annotation of contigs generated nearly 120,000 gene annotations for each species. The transcriptomes of S. fulviventer and S. hispidus were then used to assess immune response to RSV infection. We identified 238 unique genes that are significantly differentially expressed, including several genes implicated in RSV infection (e.g., Mx2, I27L2, LY6E, Viperin, Keratin 6A, ISG15, CXCL10, CXCL11, IRF9) as well as novel genes that have not previously described in RSV research (LG3BP, SYWC, ABEC1, IIGP1, CREB1). This study presents two comprehensive transcriptome references as resources for future gene expression analysis studies in the cotton rat model, as well as provides gene sequences for mechanistic characterization of molecular pathways. Overall, our results provide generalizable insights into the effect of host genetics on host-virus interactions, as well as identify new host therapeutic targets for RSV treatment and prevention.

Published
2022
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2. Microbiome disturbance and resilience dynamics of the upper respiratory tract during influenza A virus infection

Author

Drishti Kaul, Raveen Rathnasinghe, Marcela Ferres, Gene S. Tan, Aldo Barrera, Brett E. Pickett, Barbara A. Methe, Suman R. Das, Isolda Budnik, Rebecca A. Halpin, David Wentworth, Mirco Schmolke, Ignacio Mena, Randy A. Albrecht, Indresh Singh, Karen E. Nelson, Adolfo García-Sastre, Chris L. Dupont, and Rafael A. Medina

Subjects
Science
Abstract

Influenza A virus (IAV) infection can be exacerbated by bacterial co-infections but the effect of IAV on the upper respiratory tract (URT) microbiome remains unclear. Here, the authors compare the dynamics of the UTR microbiome in IAV-infected ferrets and humans, finding similar trends at the ecosystem and individual taxon level in both hosts.

Published
2020
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3. Author Correction: Microbiome disturbance and resilience dynamics of the upper respiratory tract during influenza A virus infection

Author

Drishti Kaul, Raveen Rathnasinghe, Marcela Ferres, Gene S. Tan, Aldo Barrera, Brett E. Pickett, Barbara A. Methe, Suman R. Das, Isolda Budnik, Rebecca A. Halpin, David Wentworth, Mirco Schmolke, Ignacio Mena, Randy A. Albrecht, Indresh Singh, Karen E. Nelson, Adolfo García-Sastre, Chris L. Dupont, and Rafael A. Medina

Subjects
Science
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020
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4. Author Correction: Microbiome disturbance and resilience dynamics of the upper respiratory tract during influenza A virus infection

Author

Marcela Ferrés, Indresh Singh, David E. Wentworth, Drishti Kaul, Aldo Barrera, Rafael A. Medina, Barbara Methé, Suman R. Das, Isolda Budnik, Ignacio Mena, Adolfo García-Sastre, Randy A. Albrecht, Gene S. Tan, Christopher L. Dupont, Karen E. Nelson, Mirco Schmolke, Rebecca A. Halpin, Brett E. Pickett, and Raveen Rathnasinghe

Subjects
Adult, Male, Disturbance (geology), Adolescent, Science, General Physics and Astronomy, Biology, medicine.disease_cause, Article, General Biochemistry, Genetics and Molecular Biology, Young Adult, Orthomyxoviridae Infections, Nasopharynx, Environmental health, Influenza, Human, Influenza A virus, medicine, Animals, Humans, Longitudinal Studies, Microbiome, Author Correction, Child, lcsh:Science, Resilience (network), Aged, Multidisciplinary, Bacteria, Microbiota, Ferrets, Infant, Biodiversity, General Chemistry, Middle Aged, Translational research, medicine.anatomical_structure, Child, Preschool, Dysbiosis, Female, lcsh:Q, Influenza virus, Respiratory tract
Abstract

Infection with influenza can be aggravated by bacterial co-infections, which often results in disease exacerbation. The effects of influenza infection on the upper respiratory tract (URT) microbiome are largely unknown. Here, we report a longitudinal study to assess the temporal dynamics of the URT microbiomes of uninfected and influenza virus-infected humans and ferrets. Uninfected human patients and ferret URT microbiomes have stable healthy ecostate communities both within and between individuals. In contrast, infected patients and ferrets exhibit large changes in bacterial community composition over time and between individuals. The unhealthy ecostates of infected individuals progress towards the healthy ecostate, coinciding with viral clearance and recovery. Pseudomonadales associate statistically with the disturbed microbiomes of infected individuals. The dynamic and resilient microbiome during influenza virus infection in multiple hosts provides a compelling rationale for the maintenance of the microbiome homeostasis as a potential therapeutic target to prevent IAV associated bacterial co-infections., Influenza A virus (IAV) infection can be exacerbated by bacterial co-infections but the effect of IAV on the upper respiratory tract (URT) microbiome remains unclear. Here, the authors compare the dynamics of the UTR microbiome in IAV-infected ferrets and humans, finding similar trends at the ecosystem and individual taxon level in both hosts.

Published
2020

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