Browsing by Author "Liu, Yiling"

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    Dysregulated transcriptional responses to SARS-CoV-2 in the periphery support novel diagnostic approaches.
    (medRxiv, 2020-07-26) McClain, Micah T; Constantine, Florica J; Henao, Ricardo; Liu, Yiling; Tsalik, Ephraim L; Burke, Thomas W; Steinbrink, Julie M; Petzold, Elizabeth; Nicholson, Bradly P; Rolfe, Robert; Kraft, Bryan D; Kelly, Matthew S; Sempowski, Gregory D; Denny, Thomas N; Ginsburg, Geoffrey S; Woods, Christopher W
    In order to elucidate novel aspects of the host response to SARS-CoV-2 we performed RNA sequencing on peripheral blood samples across 77 timepoints from 46 subjects with COVID-19 and compared them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a conserved transcriptomic response in peripheral blood that is heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, that persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95). The transcriptome in peripheral blood reveals unique aspects of the immune response in COVID-19 and provides for novel biomarker-based approaches to diagnosis.
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    Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.
    (Nature communications, 2021-02-17) McClain, Micah T; Constantine, Florica J; Henao, Ricardo; Liu, Yiling; Tsalik, Ephraim L; Burke, Thomas W; Steinbrink, Julie M; Petzold, Elizabeth; Nicholson, Bradly P; Rolfe, Robert; Kraft, Bryan D; Kelly, Matthew S; Saban, Daniel R; Yu, Chen; Shen, Xiling; Ko, Emily M; Sempowski, Gregory D; Denny, Thomas N; Ginsburg, Geoffrey S; Woods, Christopher W
    SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral blood samples from 46 subjects with COVID-19 and directly comparing them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a powerful transcriptomic response in peripheral blood with conserved components that are heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, which persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95 [95% CI 0.92-0.98]). The transcriptome in peripheral blood reveals both diverse and conserved components of the immune response in COVID-19 and provides for potential biomarker-based approaches to diagnosis.
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    The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood.
    (Frontiers in immunology, 2021-01) 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
    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.