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Antiviral potential of human IFN-α subtypes against influenza H3N2 infection in human lung explants

ABSTRACT: Antiviral potential of human IFN-α subtypes against influenza H3N2 infection in human lung explants

PROVIDER: PRJNA557257 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9856930_1.fastq.gz	Fastqsanger.gz
	SRR9856930_2.fastq.gz	Fastqsanger.gz
	SRR9856921_1.fastq.gz	Fastqsanger.gz
	SRR9856921_2.fastq.gz	Fastqsanger.gz
	SRR9856931_1.fastq.gz	Fastqsanger.gz

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Antiviral potential of human IFN-α subtypes against influenza H3N2 infection in human lung explants

Project description:Determining the role of interferons in the host defence against influenza A virus Methods: Tumor-free human lung explants were obtained from patients undergoing lung surgery at the University Hospital Muenster on the day of surgery. Tissue blocks were individually placed in a 12-well plate in RPMI medium. Virus infection of human lung tissue was performed with seasonal IV H3N2 strain A/Panama/2007/1999. RNA was prepared from tissue homogenates. Results: RNA sequencing revealed significant transcriptional upregulation of genes encoding IFN-α subtypes α1, α2, α8, α14 and α17, which we identified to possess only low to intermediate antiviral activity. In contrast, our experiments provide evidence that subtypes α16, α5 and α4 suppress H3N2 replication 40 – 231 fold more efficiently compared to clinically approved IFN-α2. We detected significantly higher induction of IV restriction factors MxA, RIG-I, OAS1 and PKR by these subtypes compared to the non-active IFN-α1 but correlation of antiviral activity with the expression levels of these restriction factors was not observed. Conclusions: Our results show that IFN-α subtypes differ in their ability to repress H3N2 replication in human lung tissue and emphasize that IFN-α subtypes α16, α5 and α4 have high therapeutic potential and should be further investigated for the prevention and treatment of severe infections with seasonal H3N2.

2019-12-31 | GSE135069 | GEO

Antiviral potential of human IFN-α subtypes against influenza A H3N2 infection in human lung explants reveals subtype-specific activities.

Project description:Influenza is an acute respiratory infection causing high morbidity and mortality in annual outbreaks worldwide. Antiviral drugs are limited and pose the risk of resistance development, calling for new treatment options. IFN-α subtypes are immune-stimulatory cytokines with strong antiviral activities against IAV in vitro and in vivo. However, the clinical use of IFN-α2, the only licensed subtype of this multi-gene family, could not prevent or limit IAV infections in humans. However, the other subtypes were not investigated.Therefore, this study evaluated the induction and antiviral potential of all human IFN-α subtypes during H3N2 IAV infection in human lung explants. We found that subtypes with weak antiviral activities were preferentially induced during IAV infection in human lungs. Intriguingly, non-induced subtypes α16, α5 and α4 suppressed viral replication up to 230-fold more efficiently than α2. Furthermore, our results demonstrate that subtypes with stronger antiviral activities induce higher expression of IAV-specific restriction factors and that MxA expression is a determinant of the subtype-specific antiviral activity towards H3N2 IAV. These results corroborate that IFN-α subtypes exhibit differential antiviral activities and emphasize that subtypes α16, α5 and α4 should be further investigated for the prevention and treatment of severe infections with seasonal H3N2 IAV.

| S-EPMC6913622 | biostudies-literature

Analysis of transcriptional differences after IFN-beta (IFN-b) or IFN-lambda (IFN-l) treated human mid-gestation chorionic villus explants

Project description:Purpose: Treatment of midgestation chorionic villus explants with recombinant IFN-b leads to morphological changes including formation of syncitial knots. However, treatment of explants with IFN-l, which is constitutively expressed by syncytiotrophoblasts, is not sufficient to cause these same changes. To understand the different transcriptional changes induced by IFN-b and IFN-l and underlying cause of these morphological changes, we performed RNAsequencing after these different treatments. Methods: Chorionic villi of 18-21 gestation week placentas were dissected. Explants were cultured in DMEM F/12 with 1000 U recombinant IFN-b or 1000U recombinant IFN-l for 24 hours. RNA was then isolated from explants, and RNAsequencing was performed to assess transcriptional changes. Results/ Conclusions: IFN-b but not IFN-l induces interferon stimulated genes (ISGs) in mid gestation chorionic villus explants.

2017-12-31 | GSE104348 | GEO

Host microRNA molecular signatures associated with human H1N1 and H3N2 influenza A viruses

Project description:In this study, we performed a miRNA global profiling in human lung epithelial cells (A549) infected by two different subtypes of human influenza A viruses (H1N1 and H3N2).

2013-04-03 | GSE42003 | GEO

Identification of H3N2 specific antibodies cross-reacting with H7 strains

Project description:Binding profile of H3N2 hemagglutinin (HA) reactive antibodies for various H3N2 and H7 HA proteins

2014-11-14 | GSE63249 | GEO

Inhibition of hepsin in human breast cancer explants

Project description:Human breast tumor explants were treated with the hepsin inhibitory antibody Ab25 (5μM, 48h).

2023-10-27 | GSE205774 | GEO

Role for ISGF3II in the Antiviral Activity of IFN-gamma

Project description:Type-I (e.g. IFN-alpha, IFN-beta) and type-II IFNs (IFN-gamma) have antiviral, antiproliferative, and immunomodulatory properties. Both types of IFN signal through the Jak/STAT pathway to elicit antiviral activity, yet IFN-gamma is thought to do so only through STAT1 homodimers while type-I IFNs activate both STAT1- and STAT2-containing complexes such as ISGF3. Here we show that ISGF3II - composed of phosphorylated STAT1, unphosphorylated STAT2, and IRF9 - also plays a role in IFN-gamma-mediated antiviral activity in humans. Using phosphorylated STAT1 as a marker for IFN signaling, western blot analysis of IFN-alpha2a treated human A549 cells revealed that pSTAT1 (Y701) levels peaked at 1h, decreased by 6h, and remained at low levels for up to 48h. Cells treated with IFN-gamma showed a biphasic pSTAT1 response with an early peak at 1-2h and a second peak at 15-24h. Gene expression microarray following IFN-gamma treatment for 24h indicated an induction of antiviral genes that are induced by ISGF3 and associated with a type-1 IFN response. Induction of these genes by autocrine type-I and type-III IFN signaling was ruled out using neutralizing antibodies to these IFNs in biological assays and by qRT-PCR. Despite the absence of autocrine IFNs, IFN-gamma treatment induced formation of ISGF3II. This novel transcription factor complex binds to ISRE promoter sequences, as shown by ChIP analysis of the PKR promoter. STAT2 and IRF9 knockdown in A549 cells reversed IFN-gamma-mediated ISRE induction and antiviral activity - implicating ISGF3II formation as a significant component of the cellular response and biological activity of IFN-gamma. Two treatments using three biological replicates each were performed using three million A549 cells. Each was seeded overnight in 10mL complete RPMI and treated. Three were treated with alpha-IFN and three treated with gamma-IFN for 24h. Control samples were left untreated.

2011-01-19 | E-GEOD-25113 | biostudies-arrayexpress

Quantitative single-cell transcriptome-based ranking of engineered AAVs in human retinal explants

Project description:Gene therapy is a rapidly developing field, and adeno-associated virus (AAV) is a leading viral vector candidate for therapeutic gene delivery. Newly engineered AAVs with improved abilities are now entering the clinic. It has proven challenging, however, to predict the translational potential of gene therapies developed in animal models, due to cross-species differences. Human retinal explants are the only available model of fully developed human retinal tissue, and are thus important for the validation of candidate AAV vectors. In this study, we evaluated 18 wildtype and engineered AAV capsids in human retinal explants using a recently developed single-cell RNA-Seq AAV engineering pipeline (scAAVengr). Human retinal explants retain the same major cell types as fresh retina, with similar expression of cell-specific markers, except for a photoreceptor population with altered expression of photoreceptor-specific genes. The efficiency and tropism of AAVs in human explants was quantified, with single cell resolution. The top performing serotypes, K91, K912, and 7m8, were further validated in non-human primate and human retinal explants. Together, this study provides detailed information about the transcriptome profiles of retinal explants, and quantifies the infectivity of leading AAV serotypes in human retina, accelerating the translation of retinal gene therapies to the clinic.

2022-04-28 | GSE199840 | GEO

Inhibition of hepsin in human breast cancer explants

Project description:Inhibition of hepsin in human breast cancer explants

| PRJNA847565 | ENA

Human lung tissue explants infected with influenza B virus

Project description:RNAseq analysis of human lung tissue explants infected with Influenza B virus Results: Differentially expressed genes after infection Project: Hulu_FluB_2022

2022-08-31 | GSE197143 | GEO

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