Pathogenesis, MicroRNA‐122 Gene‐Regulation, and Protective Immune Responses After Acute Equine Hepacivirus Infection

Tomlinson, Joy E.; Wolfisberg, Raphael; Fahnøe, Ulrik; Patel, Roosheel S.; Trivedi, Sheetal; Kumar, Arvind; Sharma, Himanshu; Nielsen, Louise; McDonough, Sean P.; Bukh, Jens; Tennant, Bud C.; Kapoor, Amit; Rosenberg, Brad R.; Rice, Charles M.; Divers, Thomas J.; Walle, Gerlinde R. Van de; Scheel, Troels K. H.

doi:10.1002/hep.31802

Cited by 18 publications

(46 citation statements)

References 43 publications

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“…Information about RNA extraction and library preparation [ 5 ] has been included in the Supplementary material . Differential gene analysis was performed in R, as described previously [ 6 ]. Briefly, we used the Limma-voom and DeSeq2 package for preprocessing and principal component (PC) analysis, respectively.…”

Section: Methodsmentioning

confidence: 99%

A Distinct Dexamethasone-Dependent Gene Expression Profile in the Lungs of COVID-19 Patients

Fahnøe

Ronit

Berg

et al. 2022

The Journal of Infectious Diseases

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The effects of dexamethasone (DXM) treatment on pulmonary immunity in COVID-19 associated acute respiratory distress syndrome (CARDS) remain insufficiently understood. We performed transcriptomic RNA-seq analysis of bronchoalveolar lavage fluid from 20 mechanically ventilated patients: 12 with CARDS (DXM+ or DXM-) and 8 non-COVID-19 critically ill controls. CARDS (+DXM) was characterized by upregulation of genes related to B-cell and complement pathway activation, antigen presentation, phagocytosis and FC-gamma receptor signalling. Most ISGs were upregulated in CARDS, particularly in CARDS (-DXM). In conclusion, DXM treatment was not associated with regulation of pro-inflammatory pathways in CARDS but with regulation of other local immune responses.

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Section: Methodsmentioning

confidence: 99%

A Distinct Dexamethasone-Dependent Gene Expression Profile in the Lungs of COVID-19 Patients

Fahnøe

Ronit

Berg

et al. 2022

The Journal of Infectious Diseases

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“…The absence of strong selection pressure and the low diversity could be linked to a weak humoral immune response which has previously been observed in EqHV-infected horses ( Pfaender et al. 2017 ; Tomlinson et al. 2021 ).…”

Section: Discussionmentioning

confidence: 70%

“…2015 ; Pfaender et al. 2017 ; Tomlinson et al. 2021 ), however, it was shown that foals infected with EqHV remained RNA positive for at least a year post-infection, indicating that persistent EqHV infection can be achieved by experimental inoculation.…”

Section: Discussionmentioning

confidence: 99%

Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and clearance

et al. 2022

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Even 30 years after the discovery of the hepatitis C virus (HCV) in humans there is still no vaccine available. Reasons for this include the high mutation rate of HCV, which allows the virus to escape immune recognition, and the absence of an immunocompetent animal model for vaccine development. Phylogenetically distinct hepaciviruses (genus Hepacivirus, family Flaviviridae) have been isolated from diverse species, each with a narrow host range: the equine hepacivirus (EqHV) is the closest known relative of HCV. In this study we used amplicon-based deep-sequencing to investigate the viral intra-host population composition of the genomic regions encoding the surface glycoproteins E1 and E2. Patterns of E1E2 substitutional evolution were compared in longitudinally sampled EqHV-positive sera of naturally and experimentally infected horses and HCV-positive patients. Intra-host virus diversity was higher in chronically than in acutely infected horses, a pattern which was similar in the HCV infected patients. However, overall glycoprotein variability was higher in HCV compared to EqHV. Additionally, selection pressure in HCV populations was higher, especially within the N-terminal region of E2, corresponding to the hypervariable region 1 (HVR1) in HCV. An alignment of glycoprotein sequences from diverse hepaciviruses identified the HVR1 as unique characteristic of HCV: hepaciviruses from non-human species lack this region. Together, these data indicate that EqHV infection of horses could represent a powerful surrogate animal model to gain insights into hepaciviral evolution and HCVs HVR1-mediated immune evasion strategy.

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“…Second, because it relies on direct sequencing as compared to the use of predefined probes in microarrays, it is suitable for the detection of novel genes or transcripts of interest that may not be represented on the microarray chip. Third, the direct sequencing approach makes RNA-seq highly suitable for use in surrogate animal models of different species such as the equine hepacivirus (EqHV) model [ 25 ]. Finally, RNA-seq data provide additional analysis opportunities for important biological information, e.g., the comparison of differential splicing across samples [ 26 , 27 ], functionally relevant single nucleotide polymorphism (SNP) analysis [ 28 ] and RNA editing events [ 29 , 30 , 31 ].…”

Section: Overview and Comparison Of Systems-transcriptomic Methodsmentioning

confidence: 99%

“…Comparative analyses demonstrated common signatures with those of flaviviruses yellow fever and dengue [ 53 ]. Recent RNA-seq analysis of the liver and peripheral blood of horses infected with equine hepacivirus (EqHV), which is highly related to HCV, demonstrated an ISG signature in the liver [ 25 ]. However, only minimal perturbations in adaptive immune cell signatures were detectable in the peripheral blood despite the fact that EqHV-specific T cells were identified following specific peptide stimulation [ 25 ].…”

Section: Systems Biology Studies Of the Immune Response During Acute And Chronic Hcv Infectionmentioning

confidence: 99%

Towards a Systems Immunology Approach to Understanding Correlates of Protective Immunity against HCV

Shoukry

2021

Viruses

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Over the past decade, tremendous progress has been made in systems biology-based approaches to studying immunity to viral infections and responses to vaccines. These approaches that integrate multiple facets of the immune response, including transcriptomics, serology and immune functions, are now being applied to understand correlates of protective immunity against hepatitis C virus (HCV) infection and to inform vaccine development. This review focuses on recent progress in understanding immunity to HCV using systems biology, specifically transcriptomic and epigenetic studies. It also examines proposed strategies moving forward towards an integrated systems immunology approach for predicting and evaluating the efficacy of the next generation of HCV vaccines.

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Pathogenesis, MicroRNA‐122 Gene‐Regulation, and Protective Immune Responses After Acute Equine Hepacivirus Infection

Cited by 18 publications

References 43 publications

A Distinct Dexamethasone-Dependent Gene Expression Profile in the Lungs of COVID-19 Patients

A Distinct Dexamethasone-Dependent Gene Expression Profile in the Lungs of COVID-19 Patients

Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and clearance

Towards a Systems Immunology Approach to Understanding Correlates of Protective Immunity against HCV

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