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.

Interactomics: Dozens of Viruses, Co-evolving With Humans, Including the Influenza A Virus, may Actively Distort Human Aging

“…Moreover, we used published transcriptomic data to further investigate the potential of several top age-distorter candidates to interfere with cellular senescence. We took advantage of the recent demonstration that human cellular senescence can be empirically deduced from transcriptomes through differential expression of a set of 125 biomarker genes, known as SenMayo biomarkers ( Saul et al 2022 ), to search for evidence of an alteration of cellular senescence associated with various viral infection ( Kaczkowski et al 2012 ; Jagya et al 2014 ; Peng et al 2014 ; Bercovich-Kinori et al 2016 ; Devadas et al 2016 ; Hu et al 2016 ; Tang et al 2016 ; Zhang et al 2016 ; Boldanova et al 2017 ; Deshiere et al 2017 ; Harden et al 2017 ; Hojka-Osinska et al 2017 ; Klymenko et al 2017 ; McGrath et al 2017 ; Oberstein and Shenk 2017 ; Oh et al 2017 ; Razooky et al 2017 ; Viollet et al 2017 ; Zhu et al 2017 ; Journo et al 2018 ; Tso et al 2018 ; Golumbeanu et al 2019 ; Mrozek-Gorska et al 2019 ; Wang et al 2019 ; Blanco-Melo et al 2020 ; Dissanayake et al 2020 ; Li et al 2020 ; Seelbinder et al 2020 ; Sen et al 2020 ; Sheng et al 2020 ; Thompson et al 2020 ; Winer et al 2020 ; Zhuravlev et al 2020 ; Bauby et al 2021 ; Chandrashekar et al 2021 ; Chow et al 2021 ; Coelho et al 2021 ; Dapat et al 2021 ; van der Heijden et al 2021 ; Hong et al 2021 ; Tegtmeyer et al 2021 ; Tsalik et al 2021 ; Yanagi et al 2021 ; Yuan et a...…”

Long noncoding RNA CHROMR regulates antiviral immunity in humans

“…To identify lncRNAs implicated in the host response to respiratory viruses, we performed RNA sequencing (RNA-seq) of whole blood from hospitalized patients with coronavirus disease 2019 (COVID-19) induced by SARS-CoV-2 ( n = 8) and age- and sex-matched controls ( n = 7) ( SI Appendix , Table S1 ), and compared this to whole blood transcriptomic analysis of subjects with influenza (IAV; n = 41) and controls ( n = 18) (retrieved from GSE157240 ( 21 )). Differential expression analysis revealed 830 lncRNAs altered in patients with COVID-19 and 340 changed in patients with influenza; 191 lncRNAs were dysregulated in both diseases ( P -adj < 0.05, −1.5 < fold change > 1.5; Fig.…”

“…To obtain differentially expressed transcripts between influenza A–infected patients ( n = 41) and controls ( n = 18) we queried publicly available dataset GSE157240 ( 21 ). FASTQ files from RNA-seq (influenza A and SARS-CoV-2) were processed via the Seq- N -Slide pipeline ( 40 ).…”

Indole-3-carbinol in vitro antiviral activity against SARS-Cov-2 virus and in vivo toxicity

“…Viruses cause a wide spectrum of clinical illnesses, most of which are acute respiratory infections. In most cases, the symptoms of acute respiratory infection are similar for different viruses, though the severity may be variable [ 43 ]. Respiratory viral infections represent a significant threat to human health worldwide.…”