A Host of Host Assays: The Clinical Accuracy of Two Host Gene Expression Assays in Acute Infection*

ABSTRACT Commensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions, as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However, few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here, we leverage a large study of laboratory-raised fish from the species Gasterosteus aculeatus (three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immune genes. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated with host gene expression. These families were all tightly correlated with host expression of immune genes and processes, falling into one of three categories—those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with the abundance of these taxa, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition. IMPORTANCE Here, we document associations between host gene expression and gut microbiome composition in a nonmammalian vertebrate species. We highlight associations between expression of immune genes and both microbiome diversity and abundance of specific microbial taxa. These findings support other findings from model systems which have suggested that gut microbiome composition and host immunity are intimately linked. Furthermore, we demonstrate that these correlations are truly systemic; the gene expression detailed here was collected from an important fish immune organ (the head kidney) that is anatomically distant from the gut. This emphasizes the systemic impact of connections between gut microbiota and host immune function. Our work is a significant advancement in the understanding of immune-microbiome links in nonmodel, natural systems.

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Microbiota Modulates Host Gene Expression via MicroRNAs

Gastroenterology ◽

10.1016/s0016-5085(11)62754-6 ◽

2011 ◽

Vol 140 (5) ◽

pp. S-663 ◽

Cited By ~ 2

Author(s):

Guillaume Dalmasso ◽

Hang Thi Thu Nguyen ◽

Yutao Yan ◽

Hamed Laroui ◽

Moiz A. Charania ◽

...

Keyword(s):

Gene Expression ◽

Host Gene ◽

Host Gene Expression

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Abstract 19222: Hypoxia Regulated Circular RNAs Control Endothelial Cell Functions (Best of Basic Science Abstract)

Circulation ◽

10.1161/circ.132.suppl_3.19222 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Andreas W Heumüller ◽

Jes-Niels Boeckel ◽

Nicolas Jaé ◽

Yuliya Ponomareva ◽

Wei Chen ◽

...

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Network Formation ◽

Rare Event ◽

Expression Regulation ◽

Host Gene ◽

Circular Rnas ◽

Host Gene Expression ◽

Go Annotation ◽

Cell Functions

Circular RNAs (circRNAs) are non-coding RNAs generated by back-splicing. Back-splicing has been considered as a rare event, but circRNAs were recently found to be abundantly expressed among a variety of human cells and tissues. Nevertheless, the expressional regulation, processing and biological functions of circRNAs are largely unknown. Cytoplasmic circRNAs can bind and trap microRNAs, whereas nuclear circRNAs may affect host gene expression. However, the expression, regulation and functions of circRNAs in endothelial cells have not been determined so far. In this study, basal expression and regulation of circRNAs by hypoxia in human umbilical endothelial cells (HUVEC) were analyzed using deep sequencing. Among the identified 7,388 circRNAs, 2,875 had not been annotated before. We further validated the expression of 40 selected circRNAs by RT-PCR and found that the majority is resistant to RNase R digestion, lacks polyadenylation and is localized to the cytoplasm. Cloning and subsequent sequencing validated the newly generated back splice sites for selected circRNAs. Furthermore, analysis of RNA-seq data revealed that circRNAs, particularly the cytoplasmatic circular RNA cZNF292, are significantly regulated by hypoxia in HUVECs. The siRNA-mediated knockdown of HIF-1α had no effect on cZNF292 induction under hypoxia, suggesting a HIF-1α independent regulation. Most importantly, siRNA-mediated knockdown of cZNF292 significantly reduced spheroid sprouting and network formation of endothelial cells. Furthermore, knockdown of cZNF292 had no effect on its host gene expression. Exon array analysis after cZNF292 knockdown revealed a significant expressional upregulation of 167 as well as a significant expressional downregulation of 123 genes of which most were associated with metabolic processes according to GO annotation. Analysis of Ago-HITS-CLIP data revealed no putative miR-binding sites, suggesting that cZNF292 does not act as a miR-sponge. Taken together, we show for the first time the expression, regulation and function of circRNAs in endothelial cells. The circRNA cZNF292 is regulated by hypoxia and has an important angiogenic function in endothelial cells.

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Dataset of mutational analysis, miRNAs targeting SARS-CoV-2 genes and host gene expression in SARS-CoV and SARS-CoV-2 infections

Data in Brief ◽

10.1016/j.dib.2020.106207 ◽

2020 ◽

Vol 32 ◽

pp. 106207 ◽

Cited By ~ 1

Author(s):

Rahila Sardar ◽

Deepshikha Satish ◽

Shweta Birla ◽

Dinesh Gupta

Keyword(s):

Gene Expression ◽

Mutational Analysis ◽

Host Gene ◽

Host Gene Expression

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Matrix Protein and Another Viral Component Contribute to Induction of Apoptosis in Cells Infected with Vesicular Stomatitis Virus

Journal of Virology ◽

10.1128/jvi.75.24.12169-12181.2001 ◽

2001 ◽

Vol 75 (24) ◽

pp. 12169-12181 ◽

Cited By ~ 118

Author(s):

Sarah A. Kopecky ◽

Mark C. Willingham ◽

Douglas S. Lyles

Keyword(s):

Gene Expression ◽

Caspase 3 ◽

Host Gene ◽

M Protein ◽

Host Gene Expression ◽

Bhk Cells ◽

Viral Component ◽

Induction Of Apoptosis ◽

Induced Apoptosis ◽

Viral Components

ABSTRACT The induction of apoptosis in host cells is a prominent cytopathic effect of vesicular stomatitis virus (VSV) infection. The viral matrix (M) protein is responsible for several important cytopathic effects, including the inhibition of host gene expression and the induction of cell rounding in VSV-infected cells. This raises the question of whether M protein is also involved in the induction of apoptosis. HeLa or BHK cells were transfected with M mRNA to determine whether M protein induces apoptosis when expressed in the absence of other viral components. Expression of M protein induced apoptotic morphological changes and activated caspase-3 in both cell types, indicating that M protein induces apoptosis in the absence of other viral components. An M protein containing a point mutation that renders it defective in the inhibition of host gene expression (M51R mutation) activated little, if any, caspase-3, while a deletion mutant lacking amino acids 4 to 21 that is defective in the virus assembly function but fully functional in the inhibition of host gene expression was as effective as wild-type (wt) M protein in activating caspase-3. To determine whether M protein influences the induction of apoptosis in the context of a virus infection, the M51R M protein mutation was incorporated onto a wt background by using a recombinant infectious cDNA clone (rM51R-M virus). The timing of the induction of apoptosis by rM51R-M virus was compared to that by the corresponding recombinant wt (rwt) virus and to that by tsO82 virus, the mutant virus in which the M51R mutation was originally identified. In HeLa cells, rwt virus induced apoptosis faster than did rM51R-M virus, demonstrating a role for M protein in the induction of apoptosis. In contrast to the results obtained with HeLa cells, rwt virus induced apoptosis more slowly than did rM51R-M virus in BHK cells. This indicates that a viral component other than M protein contributes to induction of apoptosis in BHK cells and that wt M protein acts to delay induction of apoptosis by the other viral component. tsO82 virus induced apoptosis more rapidly than did rM51R-M virus in both HeLa and BHK cells. These two viruses contain the same point mutation in their M proteins, suggesting that sequence differences in genes other than that for M protein affect their rates of induction of apoptosis.

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