Dynamic changes in host gene expression associated with H5N8 avian influenza virus infection in mice

Park, Su Jin; Kumar, Mukesh; Kwon, Hyeok Il; Seong, Rak Kyun; Han, Kyudong; Song, Jae Min; Kim, Chul-Joong; Choi, Young Ki; Shin, Ok Sarah

doi:10.1038/srep16512

Cited by 42 publications

(34 citation statements)

References 31 publications

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“…A better understanding of the global gene changes underlying the multi-step progression of pathogenicity during infection could help develop potential therapeutic strategies for emerging infectious diseases including WNV. Very recently, high-throughput RNA sequencing (RNA-seq) technology, which is a powerful way to profile the transcriptome with great efficiency and higher accuracy, has been employed in various viral infections and diseases 8 9 . RNA-seq technology is highly sensitive, quantitative, and provides unbiased measurement of gene transcripts in a large dynamic range of gene abundance.…”

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confidence: 99%

Identification of host genes leading to West Nile virus encephalitis in mice brain using RNA-seq analysis

Kumar

Belcaid

Nerurkar

2016

Sci Rep

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Differential host responses may be critical determinants of distinct pathologies of West Nile virus (WNV) NY99 (pathogenic) and WNV Eg101 (non-pathogenic) strains. We employed RNA-seq technology to analyze global differential gene expression in WNV-infected mice brain and to identify the host cellular factors leading to lethal encephalitis. We identified 1,400 and 278 transcripts, which were differentially expressed after WNV NY99 and WNV Eg101 infections, respectively, and 147 genes were common to infection with both the viruses. Genes that were up-regulated in infection with both the viruses were mainly associated with interferon signaling. Genes associated with inflammation and cell death/apoptosis were only expressed after WNV NY99 infection. We demonstrate that differences in the activation of key pattern recognition receptors resulted in the induction of unique innate immune profiles, which corresponded with the induction of interferon and inflammatory responses. Pathway analysis of differentially expressed genes indicated that after WNV NY99 infection, TREM-1 mediated activation of toll-like receptors leads to the high inflammatory response. In conclusion, we have identified both common and specific responses to WNV NY99 and WNV Eg101 infections as well as genes linked to potential resistance to infection that may be targets for therapeutics.

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mentioning

confidence: 99%

Identification of host genes leading to West Nile virus encephalitis in mice brain using RNA-seq analysis

Kumar

Belcaid

Nerurkar

2016

Sci Rep

Self Cite

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“…The whole filtering process was performed as previously reported . Filtered reads were mapped to the human reference genome (Ensembl release 72) using the aligner STAR v.2.3.0e .…”

Section: Methodsmentioning

confidence: 99%

“…For differential expression analysis, gene level count data were generated using HTSeq‐count v0.5.4p3 tool with the option “‐m intersection‐nonempty” and option considering paired‐end sequence as previously reported . Based on the calculated read count data, differentially expressed genes (DEGs) were identified using the R package called TCC .…”

Section: Methodsmentioning

confidence: 99%

CD276 (B7-H3) Maintains Proliferation and Regulates Differentiation in Angiogenic Function in Late Endothelial Progenitor Cells

2018

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Endothelial progenitor cells (EPCs) provide an important source of recovery from blood vessel dysfunction. Late EPCs (LEPCs) are circulating blood cells that are capable of promoting vascular repair. Using transcriptome analysis, we identified distinctive LEPC profiles and found that CD276 (B7‐H3) mRNA is strongly expressed in LEPCs. CD276 protein is present abundantly on the cell surface of LEPC when analyzed by fluorescence‐activated cell sorter and immunocytochemistry. CD276, a B7 family member, is a type I transmembrane glycoprotein. The role of CD276 in LEPCs remains unknown. CD276 knockdown by lentivirus transduction in LEPCs significantly decreased proliferation and increased apoptosis of LEPCs in vitro. After CD276 silencing, the cell cycle of LEPCs was prone to remain at the G0/G1 phase, and the cell migration rates as well as transwell and wound‐healing migration were decreased. CD276 knockdown in LEPCs increased the G1 phase regulators cyclin D2/D3/E1‐cyclin‐dependent kinases (CDK2/4/6), but decreased the S‐G2‐M phase regulators cyclin A/B‐CDK1. However, LEPCs with CD276 knockdown resulted in increased tube formation in vitro and angiogenesis in a Matrigel plug assay in vivo. FoxC1/C2, an upstream signal of Notch in arterial cell proliferation, and Hey1/2, which is known to promote arterial differentiation in the vasculature, were upregulated in CD276 knockdown LEPCs. In LEPCS, CD276 has a positive effect on proliferation and migration of endothelial cells, but negative effects on angiogenesis, particularly endothelial cell differentiation. Our data indicate, for therapeutic purpose, that CD276 can be used to acquire and maintain cell populations of LEPCs and blocking CD276 will promote angiogenetic differentiation. We found that CD276 (B7‐H3) is enriched on the cell membrane of LEPCs. CD276 knockdown reduced proliferation and migration of LEPCs by increasing cell cycle inhibitors such as p21cip1 and pRb and decreasing pErk1/2 and pAkt but promoted angiogenesis and endothelial cell differentiation by elevating vascular endothelial growth factor‐vascular endothelial growth factor receptor 1 and p‐p38. Stem Cells 2019;37:382–394

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“…Canonical pathways and functional processes of biological importance were assessed using the list of differentially expressed genes identified by RNA-seq and the IPA Knowledge Base, as described previously 43 . Pathway enrichment p-values (Fisher's exact test) and activation z-scores were calculated by IPA.…”

Section: Pathway Analysismentioning

confidence: 99%

Transcriptome Profile of Nicotinic Receptor-Linked Sensitization of Beta Amyloid Neurotoxicity

Arora

Belcaid

Lantz

et al. 2020

Sci Rep

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Understanding the specific gene changes underlying the prodromic stages of Alzheimer's disease pathogenesis will aid the development of new, targeted therapeutic strategies for this neurodegenerative disorder. Here, we employed RNA-sequencing to analyze global differential gene expression in a defined model nerve cell line expressing α4β2 nicotinic receptors (nAChRs), high-affinity targets for beta amyloid (Aβ). The nAChR-expressing neuronal cells were treated with nanomolar Aβ 1-42 to gain insights into the molecular mechanisms underlying Aβ-induced neurotoxicity in the presence of this sensitizing target receptor. We identified 15 genes (out of 15,336) that were differentially expressed upon receptor-linked Aβ treatment. Genes up-regulated with Aβ treatment were associated with calcium signaling and axonal vesicle transport (including the α4 nAChR subunit, the calcineurin regulator RCAN3, and KIF1C of the kinesin family). Downregulated genes were associated with metabolic, apoptotic or DNA repair pathways (including APBA3, PARP1 and RAB11). Validation of the differential expression was performed via qRT-PCR and immunoblot analysis in the defined model nerve cell line and primary mouse neurons. Further verification was performed using immunocytochemistry. In conclusion, we identified apparent changes in gene expression on Aβ treatment in the presence of the sensitizing nAChRs, linked to early-stage Aβ-induced neurotoxicity, which may represent novel therapeutic targets. Amyloid-β (Aβ) is a short, potentially neurotoxic peptide derived from amyloid precursor protein (APP) in select regions of the brain 1,2. At "physiological" levels (pM), there is considerable evidence for Aβ functioning as a positive neuromodulator 3-7 , acting through neuronal signaling receptors. In Alzheimer's disease (AD), a progressive neurodegenerative disorder that is the most prevalent cause of dementia, histopathology is mainly characterized by extracellular plaques composed primarily of the Aβ peptide in fibrillar form, intracellular neurofibrillary tangles formed from hyperphosphorylated tau, and neuronal degeneration including extensive loss of cholinergic basal forebrain neurons. In addition, synaptic impairment and loss are central to changes in memory and cognition in AD 8. Notably, during the prodromic phase of AD, soluble oligomeric Aβ levels are dramatically increased (high nM to μM) years before diagnosis (see 9). There is ample evidence that it is the diffusible oligomeric Aβ assemblies that play a role in neurotoxicity 10 and contribute to driving development of synaptic impairment and degeneration, largely through induction of abnormal tau and, later, neuroinflammation 11,12. There remain important questions, however, in regard to the impact of elevated Aβ levels on neuronal function, integrity and viability, in particular altered signaling through known target receptors. Despite extensive understanding of the pathology of AD, differential diagnosis of the disease in the prodromic and early stages has been problematic, part...

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Dynamic changes in host gene expression associated with H5N8 avian influenza virus infection in mice

Cited by 42 publications

References 31 publications

Identification of host genes leading to West Nile virus encephalitis in mice brain using RNA-seq analysis

Identification of host genes leading to West Nile virus encephalitis in mice brain using RNA-seq analysis

CD276 (B7-H3) Maintains Proliferation and Regulates Differentiation in Angiogenic Function in Late Endothelial Progenitor Cells

Transcriptome Profile of Nicotinic Receptor-Linked Sensitization of Beta Amyloid Neurotoxicity

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