Evidence map›Paper›PMID 40537790›Full record

ArticleCell communication and signaling : CCS2025

Differential impact of hepatitis delta virus replication and expression of viral antigens on the cellular kinome profile.

Keerthihan Thiyagarajah, Mirco Glitscher, Kai-Henrik Peiffer, Eberhard Hildt

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Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

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3citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Keerthihan Thiyagarajah *Paul-Ehrlich-Institut, Research Group, D-63325, Langen, Germany.
Mirco Glitscher *Paul-Ehrlich-Institut, Research Group, D-63325, Langen, Germany.
Kai-Henrik PeifferDivision Gastroenterology, University Hospital Münster, Münster, Germany.
Eberhard HildtPaul-Ehrlich-Institut, Research Group, D-63325, Langen, Germany. eberhard.hildt@guest.hpi.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAn infection with hepatitis D virus (HDV) is considered the most extreme form of viral hepatitis. Infection with HDV elicits strong increases in inflammation and hepatic injury, therefore pushing liver cirrhosis and development of hepatocellular carcinoma (HCC). Despite this, little is known on how HDV influences the host-cell's equilibrium. As the pathogenesis is majorly driven by host-responses, a deep understanding is required in terms of how signalling cascades are modulated by the virus in order to identify targets for preventive and therapeutic strategies. Accordingly, this study aims to establish the kinome profile for HDAg-expressing and HDV-replicating cells which could serve as base for future research characterizing HDV-host interaction.

methodsWe performed kinome profiling in Huh7 cells ectopically expressing the two HDV protein isoforms S- and LHDAg or replicating HDV genomes. Significantly deregulated kinases were identified using an array-based screening.

resultsThe different HDAg isoforms revealed a differential impact on the overall signalling landscape predominantly in nucleoplasm. Enrichment analyses indicated that HDAg and HDV-replication elicit kinomic changes overlapping with footprints of several diseases such as viral carcinogenesis and HCC. The responsible kinases therefore present promising targets of intervention. Moreover, pathways of innate immunity, inflammation, growth-factor-response yet also distinct modulatory signalling cascades were identified. Most prominently, the MAPK- and PI3K-Akt-cascades were affected by all experimental conditions. Within these cascades AKT1, GSK3A and PRKACA were identified as the most influential hits. A hierarchical pathway map of identified deregulated kinases indicated major changes in inflammatory processes, cell cycle control and metabolic control.

conclusionsA detailed analysis of the impact of HDV on the cellular kinome was established. Based on this, host-factors, single hits and even entire signalling cascades were identified. These advance understanding of HDV life cycle, and support development of novel therapeutics, yet also help to assess pathogenic processes.

Indexed as

Antigens, ViralHepatitis delta AntigensHepatitis Delta VirusVirus ReplicationCell Line, TumorHepatitis DHumansSignal TransductionAntigens, ViralHepatitis delta AntigensHepatitis D virusHost-factorsLHDAgPathway analysisSHDAgViral life cycleVirus-host interplay

Identifiers

PMID40537790
PMCPMC12180150

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.