scholarly journals Comparative Study of SARS-CoV-2, SARS-CoV-1, MERS-CoV, HCoV-229E and Influenza Host Gene Expression in Asthma: Importance of Sex, Disease Severity, and Epithelial Heterogeneity

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1081
Author(s):  
Mackenzie E. Coden ◽  
Lucas F. Loffredo ◽  
Hiam Abdala-Valencia ◽  
Sergejs Berdnikovs
Keyword(s):  
Gene Expression ◽  
Viral Entry ◽  
Viral Infections ◽  
Differential Susceptibility ◽  
Asthma Severity ◽  
Host Gene Expression ◽  
Ciliated Cells ◽  
Human Coronavirus ◽  
Potential Factors ◽  
Viral Receptors

Epithelial characteristics underlying the differential susceptibility of chronic asthma to SARS-CoV-2 (COVID-19) and other viral infections are currently unclear. By revisiting transcriptomic data from patients with Th2 low versus Th2 high asthma, as well as mild, moderate, and severe asthmatics, we characterized the changes in expression of human coronavirus and influenza viral entry genes relative to sex, airway location, and disease endotype. We found sexual dimorphism in the expression of SARS-CoV-2-related genes ACE2, TMPRSS2, TMPRSS4, and SLC6A19. ACE2 receptor downregulation occurred specifically in females in Th2 high asthma, while proteases broadly assisting coronavirus and influenza viral entry, TMPRSS2, and TMPRSS4, were highly upregulated in both sexes. Overall, changes in SARS-CoV-2-related gene expression were specific to the Th2 high molecular endotype of asthma and different by asthma severity and airway location. The downregulation of ACE2 (COVID-19, SARS) and ANPEP (HCoV-229E) viral receptors wascorrelated with loss of club and ciliated cells in Th2 high asthma. Meanwhile, the increase in DPP4 (MERS-CoV), ST3GAL4, and ST6GAL1 (influenza) was associated with increased goblet and basal activated cells. Overall, this study elucidates sex, airway location, disease endotype, and changes in epithelial heterogeneity as potential factors underlying asthmatic susceptibility, or lack thereof, to SARS-CoV-2.

scholarly journals Comparative Study of Epithelial Entry Gene Expression of SARS-Cov-2 and Other Human Viral Species in Asthma: Differences by Sex, Airway Location Aand Disease Endotype

2021 ◽  
Author(s):  
Mackenzie Coden ◽  
Lucas Loffredo ◽  
Hiam Abdala-Valencia ◽  
Sergejs Berdnikovs
Keyword(s):  
Gene Expression ◽  
Viral Entry ◽  
Viral Infections ◽  
Differential Susceptibility ◽  
Asthma Severity ◽  
Chronic Asthma ◽  
Ciliated Cells ◽  
Human Coronavirus ◽  
Transcriptomic Data ◽  
Viral Receptors

Epithelial characteristics underlying the differential susceptibility of chronic asthma to SARS-CoV-2 (COVID-19) and other viral infections are currently unclear. By revisiting transcriptomic data from patients with Th2 low versus Th2 high asthma, as well as mild, moderate and severe asthmatics, we characterized the changes in expression of human coronavirus and influenza viral entry genes relative to sex, airway location and disease endotype. We found sexual dimorphism in expression of COVID-19 genes ACE2, TMPRSS2, TMPRSS4, and SLC6A19. ACE2 receptor downregulation occurred specifically in females in Th2 high asthma, while proteases broadly assisting coronavirus and influenza viral entry, TMPRSS2 and TMPRSS4, were highly upregulated in both sexes. Overall, changes in COVID-19 gene expression were specific to Th2 high molecular endotype of asthma, and different by asthma severity and airway location. The downregulation of ACE2 (COVID-19, SARS) and ANPEP (HCoV-229E) viral receptors correlated with loss of club and ciliated cells in Th2 high asthma, while the increase in DPP4 (MERS-CoV), ST3GAL4, and ST6GAL1 (influenza) associated with an increase in goblet and basal activated cells. Overall, this study elucidates sex, airway location, disease endotype and changes in epithelial heterogeneity as factors underlying asthmatic susceptibility, or lack thereof, to COVID-19.

scholarly journals Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253458
Author(s):  
George Mpekoulis ◽  
Efseveia Frakolaki ◽  
Styliani Taka ◽  
Anastasios Ioannidis ◽  
Alice G. Vassiliou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Infections ◽  
Dopa Decarboxylase ◽  
Nasopharyngeal Swab ◽  
Specific Cell ◽  
Mrna Levels ◽  
Host Gene Expression ◽  
Mediated Effects ◽  
Nasopharyngeal Tissue ◽  
Infected Cells

L-Dopa decarboxylase (DDC) is the most significantly co-expressed gene with ACE2, which encodes for the SARS-CoV-2 receptor angiotensin-converting enzyme 2 and the interferon-inducible truncated isoform dACE2. Our group previously showed the importance of DDC in viral infections. We hereby aimed to investigate DDC expression in COVID-19 patients and cultured SARS-CoV-2-infected cells, also in association with ACE2 and dACE2. We concurrently evaluated the expression of the viral infection- and interferon-stimulated gene ISG56 and the immune-modulatory, hypoxia-regulated gene EPO. Viral load and mRNA levels of DDC, ACE2, dACE2, ISG56 and EPO were quantified by RT-qPCR in nasopharyngeal swab samples from COVID-19 patients, showing no or mild symptoms, and from non-infected individuals. Samples from influenza-infected patients were analyzed in comparison. SARS-CoV-2-mediated effects in host gene expression were validated in cultured virus-permissive epithelial cells. We found substantially higher gene expression of DDC in COVID-19 patients (7.6-fold; p = 1.2e-13) but not in influenza-infected ones, compared to non-infected subjects. dACE2 was more elevated (2.9-fold; p = 1.02e-16) than ACE2 (1.7-fold; p = 0.0005) in SARS-CoV-2-infected individuals. ISG56 (2.5-fold; p = 3.01e-6) and EPO (2.6-fold; p = 2.1e-13) were also increased. Detected differences were not attributed to enrichment of specific cell populations in nasopharyngeal tissue. While SARS-CoV-2 virus load was positively associated with ACE2 expression (r≥0.8, p<0.001), it negatively correlated with DDC, dACE2 (r≤−0.7, p<0.001) and EPO (r≤−0.5, p<0.05). Moreover, a statistically significant correlation between DDC and dACE2 expression was observed in nasopharyngeal swab and whole blood samples of both COVID-19 and non-infected individuals (r≥0.7). In VeroE6 cells, SARS-CoV-2 negatively affected DDC, ACE2, dACE2 and EPO mRNA levels, and induced cell death, while ISG56 was enhanced at early hours post-infection. Thus, the regulation of DDC, dACE2 and EPO expression in the SARS-CoV-2-infected nasopharyngeal tissue is possibly related with an orchestrated antiviral response of the infected host as the virus suppresses these genes to favor its propagation.

scholarly journals Host Gene Expression of Macrophages in Response to Feline Coronavirus Infection

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1431 ◽  
Author(s):  
Yvonne Drechsler ◽  
Elton J. R. Vasconcelos ◽  
Lisa M. Griggs ◽  
Pedro P. P. V. Diniz ◽  
Ellen Collisson
Keyword(s):  
Gene Expression ◽  
Viral Infections ◽  
Ex Vivo ◽  
Host Gene ◽  
Host Responses ◽  
Host Gene Expression ◽  
Feline Infectious Peritonitis ◽  
Host Immune Responses ◽  
Individual Host ◽  
Feline Coronavirus

Feline coronavirus is a highly contagious virus potentially resulting in feline infectious peritonitis (FIP), while the pathogenesis of FIP remains not well understood, particularly in the events leading to the disease. A predominant theory is that the pathogenic FIPV arises from a mutation, so that it could replicate not only in enterocytes of the intestines but also in monocytes, subsequently systemically transporting the virus. The immune status and genetics of affected cats certainly play an important role in the pathogenesis. Considering the importance of genetics and host immune responses in viral infections, the goal of this study was to elucidate host gene expression in macrophages using RNA sequencing. Macrophages from healthy male cats infected with FIPV 79-1146 ex vivo displayed a differential host gene expression. Despite the virus uptake, aligned viral reads did not increase from 2 to 17 h. The overlap of host gene expression among macrophages from different cats was limited, even though viral transcripts were detected in the cells. Interestingly, some of the downregulated genes in all macrophages were involved in immune signaling, while some upregulated genes common for all cats were found to be inhibiting immune activation. Our results highlight individual host responses playing an important role, consistent with the fact that few cats develop feline infectious peritonitis despite a common presence of enteric FCoV.

scholarly journals 1218. Comparing the Diagnostic Accuracy of Clinician Judgement to a Novel Host Response Diagnostic for Acute Respiratory Illness

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S630-S630
Author(s):  
Ian S Jaffe ◽  
Anja K Jaehne ◽  
Eugenia Quackenbush ◽  
Micah T McClain ◽  
Geoffrey S Ginsburg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diagnostic Accuracy ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Treatment Plan ◽  
Respiratory Illness ◽  
Host Gene ◽  
Host Gene Expression ◽  
Net Benefit ◽  
Material Support

Abstract Background Discriminating bacterial and viral infections remains clinically challenging. The resulting antibacterial misuse contributes to antimicrobial resistance. Host gene expression-based tests are a promising strategy to discriminate of bacterial and viral infections, but their potential clinical utility has not yet been evaluated. Methods A host gene expression biosignature was measured using either qRT-PCR or microarray in 683 ED subjects with suspected infection. Based on chart reviews, we recorded clinical diagnosis as defined both by the provider assessment and by the provider treatment plan. The biosignature, diagnosis, treatment plan, and procalcitonin were compared to clinical adjudication as the reference standard. With this as a baseline, we then calculated average weighted accuracy (AWA) and change in overall net benefit (∆NB), weighting bacterial false negatives four times more seriously than false positives. Results Gene expression correctly classified the three possible disease etiologies (bacterial, viral, or non-infectious) 76.1% of the time, outperforming provider diagnosis, provider treatment, and procalcitonin (Table 1). Overall accuracy was higher in subjects with bacterial infections (n=278, 83.8% accurate) compared to those with viral (n=234, 76.5%) and non-infectious (n=171, 63.2%) etiologies. Due to a strong sensitivity bias to treat bacterial infections at the expense of diagnostic accuracy and specificity, the provider diagnosis was overall more accurate than the corresponding treatment plan (71.4% accuracy vs. 68.1%), resulting in inappropriate antibiotic use in 41.0% of cases where antibiotics were prescribed. The gene expression test had significantly higher AWA for the diagnosis of bacterial infection than both procalcitonin and provider treatment (82.4% vs. 70.3% and 74.4%, respectively; p &lt; 0.0001). Consequently, the host gene expression test had greater net benefit than provider treatment (∆NBbact = 9.9%), provider diagnosis (∆NBbact = 4.4%), and procalcitonin (∆NBbact = 27.1%). Table 1: Summary of provider, procalcitonin, and host gene expression test performance in a cohort of 683 subjects. Conclusion Host gene expression-based tests to distinguish bacterial and viral infection can facilitate more appropriate treatment, leading to improved patient outcomes and mitigating the antibiotic resistance crisis. Disclosures Geoffrey S. Ginsburg, MD PhD, Predigen, Inc (Shareholder, Other Financial or Material Support) Ephraim L. Tsalik, MD, MHS, PhD, Predigen (Shareholder, Other Financial or Material Support, Founder)

scholarly journals Suppression of Proinflammatory Signal Transduction and Gene Expression by the DualNucleic Acid Binding Domains of the Vaccinia Virus E3L Proteins

2006 ◽  
Vol 80 (20) ◽  
pp. 10083-10095 ◽  
Author(s):  
Jeffrey O. Langland ◽  
John C. Kash ◽  
Victoria Carter ◽  
Matthew J. Thomas ◽  
Michael G. Katze ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Vaccinia Virus ◽  
Cellular Response ◽  
Viral Infections ◽  
Host Gene ◽  
Host Gene Expression ◽  
Danger Signals ◽  
Binding Domains ◽  
Z Dna

ABSTRACT Cells have evolved elaborate mechanisms to counteract the onslaught of viral infections. To activate these defenses, the viral threat must be recognized. Danger signals, or pathogen-associated molecular patterns, that are induced by pathogens include double-stranded RNA (dsRNA), viral single-stranded RNA, glycolipids, and CpG DNA. Understanding the signal transduction pathways activated and host gene expression induced by these danger signals is vital to understanding virus-host interactions. The vaccinia virus E3L protein is involved in blocking the host antiviral response and increasing pathogenesis, functions that map to separate C-terminal dsRNA- and N-terminal Z-DNA-binding domains. Viruses containing mutations in these domains allow modeling of the role of dsRNA and Z-form nucleic acid in the host response to virus infection. Deletions in the Z-DNA- or dsRNA-binding domains led to activation of signal transduction cascades and up-regulation of host gene expression, with many genes involved in the inflammatory response. These data suggest that poxviruses actively inhibit cellular recognition of viral danger signals and the subsequent cellular response to the viral threat.

scholarly journals 2018. Host Gene Expression Classifiers Distinguish Bacterial and Viral Infections in Sri Lankan Patients with Acute Febrile Respiratory Illness

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S588-S588
Author(s):  
L Gayani Tillekeratne ◽  
Sunil Suchindran ◽  
Emily Ko ◽  
Elizabeth Petzold ◽  
Champica K Bodinayake ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Infections ◽  
Respiratory Illness ◽  
Host Gene ◽  
Sri Lankan ◽  
Host Gene Expression ◽  
Febrile Respiratory Illness

tiRNAs & tRFs Biogenesis and Regulation of Diseases: A Review

2019 ◽  
Vol 26 (31) ◽  
pp. 5849-5861 ◽  
Author(s):  
Pan Jiang ◽  
Feng Yan
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Metabolic Diseases ◽  
Viral Infections ◽  
Regulatory Mechanisms ◽  
Biological Functions ◽  
Reverse Transcriptases ◽  
Dna Damage Responses ◽  
Potential Applications ◽  
Viral Reverse Transcriptases

tiRNAs & tRFs are a class of small molecular noncoding tRNA derived from precise processing of mature or precursor tRNAs. Most tiRNAs & tRFs described originate from nucleus-encoded tRNAs, and only a few tiRNAs and tRFs have been reported. They have been suggested to play important roles in inhibiting protein synthesis, regulating gene expression, priming viral reverse transcriptases, and the modulation of DNA damage responses. However, the regulatory mechanisms and potential function of tiRNAs & tRFs remain poorly understood. This review aims to describe tiRNAs & tRFs, including their structure, biological functions and subcellular localization. The regulatory roles of tiRNAs & tRFs in translation, neurodegeneration, metabolic diseases, viral infections, and carcinogenesis are also discussed in detail. Finally, the potential applications of these noncoding tRNAs as biomarkers and gene regulators in different diseases is also highlighted.

scholarly journals Publisher Correction: Exogenously overexpressed intronic long noncoding RNAs activate host gene expression by affecting histone modification in Arabidopsis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhang-Wei Liu ◽  
Nan Zhao ◽  
Yin-Na Su ◽  
Shan-Shan Chen ◽  
Xin-Jian He
Keyword(s):  
Gene Expression ◽  
Histone Modification ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Host Gene ◽  
Host Gene Expression

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

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