The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood.
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 articleSubject
T-LymphocytesHumans
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
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https://hdl.handle.net/10161/24293Published Version (Please cite this version)
10.3389/fimmu.2021.741837Publication 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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Show full item recordScholars@Duke
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.
Emily Ray Ko
Assistant Professor of Medicine
Clinical and translational research, COVID-19 therapeutics, clinical biomarkers for
infectious disease.
Micah Thomas McClain
Associate Professor of Medicine
Megan Elizabeth Reller
Associate Professor of Medicine
Gayani Tillekeratne
Assistant Professor of Medicine
Global healthAntimicrobial resistance/ stewardshipAcute respiratory tract infections Emerging
infections/ dengue
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
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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