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The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood.

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Date
2021-01
Authors
Tsalik, Ephraim L
Fiorino, Cassandra
Aqeel, Ammara
Liu, Yiling
Henao, Ricardo
Ko, Emily R
Burke, Thomas W
Reller, Megan E
Bodinayake, Champica K
Nagahawatte, Ajith
Arachchi, Wasantha K
Devasiri, Vasantha
Kurukulasooriya, Ruvini
McClain, Micah T
Woods, Christopher W
Ginsburg, Geoffrey S
Tillekeratne, L Gayani
Schughart, Klaus
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(18 total)
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Abstract
Viruses cause a wide spectrum of clinical disease, the majority being acute respiratory infections (ARI). In most cases, ARI symptoms are similar for different viruses although severity can be variable. The objective of this study was to understand the shared and unique elements of the host transcriptional response to different viral pathogens. We identified 162 subjects in the US and Sri Lanka with infections due to influenza, enterovirus/rhinovirus, human metapneumovirus, dengue virus, cytomegalovirus, Epstein Barr Virus, or adenovirus. Our dataset allowed us to identify common pathways at the molecular level as well as virus-specific differences in the host immune response. Conserved elements of the host response to these viral infections highlighted the importance of interferon pathway activation. However, the magnitude of the responses varied between pathogens. We also identified virus-specific responses to influenza, enterovirus/rhinovirus, and dengue infections. Influenza-specific differentially expressed genes (DEG) revealed up-regulation of pathways related to viral defense and down-regulation of pathways related to T cell and neutrophil responses. Functional analysis of entero/rhinovirus-specific DEGs revealed up-regulation of pathways for neutrophil activation, negative regulation of immune response, and p38MAPK cascade and down-regulation of virus defenses and complement activation. Functional analysis of dengue-specific up-regulated DEGs showed enrichment of pathways for DNA replication and cell division whereas down-regulated DEGs were mainly associated with erythrocyte and myeloid cell homeostasis, reactive oxygen and peroxide metabolic processes. In conclusion, our study will contribute to a better understanding of molecular mechanisms to viral infections in humans and the identification of biomarkers to distinguish different types of viral infections.
Type
Journal article
Subject
T-Lymphocytes
Humans
Viruses
Respiratory Tract Infections
Virus Diseases
Interferons
Cohort Studies
MAP Kinase Signaling System
Immunity
Complement Activation
Oxidative Stress
Adolescent
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Young Adult
Transcriptome
Permalink
https://hdl.handle.net/10161/24293
Published Version (Please cite this version)
10.3389/fimmu.2021.741837
Publication Info
Tsalik, Ephraim L; Fiorino, Cassandra; Aqeel, Ammara; Liu, Yiling; Henao, Ricardo; Ko, Emily R; ... Schughart, Klaus (2021). The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood. Frontiers in immunology, 12. pp. 741837. 10.3389/fimmu.2021.741837. Retrieved from https://hdl.handle.net/10161/24293.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Ginsburg

Geoffrey Steven Ginsburg

Adjunct Professor in the Department of Medicine
Dr. Geoffrey S. Ginsburg's research interests are in the development of novel paradigms for developing and translating genomic information into medical practice and the integration of personalized medicine into health care.
Ko

Emily Ray Ko

Assistant Professor of Medicine
Clinical and translational research, COVID-19 therapeutics, clinical biomarkers for infectious disease.
McClain

Micah Thomas McClain

Associate Professor of Medicine
Reller

Megan Elizabeth Reller

Associate Professor of Medicine
Tillekeratne

Gayani Tillekeratne

Assistant Professor of Medicine
Global healthAntimicrobial resistance/ stewardshipAcute respiratory tract infections Emerging infections/ dengue
Tsalik

Ephraim Tsalik

Adjunct Associate Professor in the Department of Medicine
My research at Duke has focused on understanding the dynamic between host and pathogen so as to discover and develop host-response markers that can diagnose and predict health and disease.  This new and evolving approach to diagnosing illness has the potential to significantly impact individual as well as public health considering the rise of antibiotic resistance. With any potential infectious disease diagnosis, it is difficult, if not impossible, to determine at the time of pre
Woods

Christopher Wildrick Woods

Wolfgang Joklik Distinguished Professor of Global Health
1. Emerging Infections 2. Global Health 3. Epidemiology of infectious diseases 4. Clinical microbiology and diagnostics 5. Bioterrorism Preparedness 6. Surveillance for communicable diseases 7. Antimicrobial resistance
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