GeneSet Information

Tier III GS409620 • Differential gene expression within Huh7.5JFH1 cell line of fentanyl treated vs control human liver cells_pvalue

DESCRIPTION:

Differential mRNA expression of liver cells exposed to fentanyl vs control in human liver cells. The Huh7.5JFH1 and HepG2.2.15 hepatocyte cell lines were seeded at 500,000 cells per well. Fentanyl or carfentanil was added to culture medium after 24 hours. After 24 hours of incubation with drug, hepatitis C virus (HCV) core (ng/mL), or hepatitis B surface antigen (HBsAg) (ng/mL) was quantified in culture supernatants. Differential expression was assessed using moderated t-tests with a cutoff of p < 0.05 and fold change > 1.25. Transcripts meeting significance criteria were submitted to ToppGene and ToppCluster for ontological analyses. RNAseq data are available through GEO using accession number GSE167922. Differential expression of mRNA in fentanyl treated vs control cells was analyzed for each cell line using the GEO2R tool.

LABEL:

DEG Huh7.5JFH1 liver cells fentanyl vs control_pvalue

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.5

GENES IN THRESHOLD:

6751

DATE ADDED:

2024-12-05

DATE UPDATED:

2025-06-19

SPECIES:

AUTHORS:

Ling Kong, Rebekah Karns, Mohamed Tarek M Shata, Jennifer L Brown, Michael S Lyons, Kenneth E Sherman, Jason T Blackard

TITLE:

The synthetic opioid fentanyl enhances viral replication in vitro

JOURNAL:

PLoS One Apr 2021, Vol 16, pp.

ABSTRACT:

The US is in the midst of a major drug epidemic fueled in large part by the widespread recreational use of synthetic opioids such as fentanyl. Persons with opioid use disorder are at significant risk for transmission of injection-associated infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV). Commonly abused substances may antagonize immune responses and promote viral replication. However, the impact of synthetic opioids on virus replication has not been well explored. Thus, we evaluated the impact of fentanyl and carfentanil using in vitro systems that replicate infectious viruses. Fentanyl was used in cell lines replicating HBV or HCV at concentrations of 1 ng, 100 ng, and 10 ug. Viral protein synthesis was quantified by ELISA, while apoptosis and cell death were measured by M30 or MTT assays, respectively. HCV replicative fitness was evaluated in a luciferase-based system. RNAseq was performed to evaluate cellular gene regulation in the presence of fentanyl. Low dose fentanyl had no impact on HCV replication in Huh7.5JFH1 hepatocytes; however, higher doses significantly enhanced HCV replication. Similarly, a dose-dependent increase in HCV replicative fitness was observed in the presence of fentanyl. In the HepG2.2.15 hepatocyte cell line, fentanyl caused a dose-dependent increase in HBV replication, although only a higher doses than for HCV. Addition of fentanyl resulted in significant apoptosis in both hepatocyte cell lines. Cell death was minimal at low drug concentrations. RNAseq identified a number of hepatocyte genes that were differentially regulated by fentanyl, including those related to apoptosis, the antiviral / interferon response, chemokine signaling, and NFκB signaling. Collectively, these data suggest that synthetic opioids promote viral replication but may have distinct effects depending on the drug dose and the viral target. As higher viral loads are associated with pathogenesis and virus transmission, additional research is essential to an enhanced understanding of opioid-virus pathogenesis and for the development of new and optimized treatment strategies. PUBMED: 33852610
Find other GeneSets from this publication

Annotation Information

No sequence read archive data associated with this GeneSet.


Social Control, Formal (D012926)
Cell Line (D002460)
Hepacivirus (D016174)
Humans (D006801)
Fentanyl (D005283)
Immunity (D007109)
Death (D003643)
Antigens (D000941)
Hepatocytes (D022781)
Herpesvirus 1, Cercopithecine (D006568)
Hepatitis B virus (D006515)
Opioid-Related Disorders (D009293)
RNA, Messenger (D012333)
Enzyme-Linked Immunosorbent Assay (D004797)
Proteins (D011506)
Therapeutics (D013812)
Liver (D008099)
Risk (D012306)
Culture (D003469)
Viral Proteins (D014764)
Hepatitis (D006505)
Hepatitis B (D006509)
Pharmaceutical Preparations (D004364)
Antigens, Surface (D000954)
Viruses (D014780)
Interferons (D007372)
Cells (D002477)
Cell Death (D016923)
Infection (D007239)
Hepatitis C (D006526)
Chemokines (D018925)
Hepatitis B Surface Antigens (D006514)
Injections (D007267)
Luciferases (D008156)
Virus Replication (D014779)
Analgesics, Opioid (D000701)
Apoptosis (D017209)
Antiviral Agents (D000998)
liver (MA:0000358)
liver inflammation (MP:0001860)
killing by symbiont of host cells (GO:0001907)
apoptosis (GO:0006915)
cell death (GO:0008219)
biological regulation (GO:0065007)
modulation by symbiont of host defense response (GO:0052031)
modification by symbiont of host morphology or physiology (GO:0044003)
cytolysis by symbiont of host cells (GO:0001897)
viral nucleocapsid (GO:0019013)
biosynthetic process (GO:0009058)
viral genome replication (GO:0019079)
developmental process (GO:0032502)
viral protein biosynthetic process (GO:0019081)
hemolysis by symbiont of host erythrocytes (GO:0019836)
viral infectious cycle (GO:0019058)
regulation of gene expression (GO:0010468)
signaling (GO:0023052)
translation (GO:0006412)
positive regulation by symbiont of host programmed cell death (GO:0052042)
Developmental biology resources (EDAM_topic:3064)
Genetics (EDAM_topic:3053)
Cell biology resources (EDAM_topic:2229)
protein (EDAM_format:1208)
Gene regulation (EDAM_topic:0204)
Transcriptomics (EDAM_topic:0203)
fentanyl (CHEBI:119915)
protein (CHEBI:36080)
antigen (CHEBI:59132)
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (CHEBI:53233)
drug (CHEBI:23888)
protein polypeptide chain (CHEBI:16541)
messenger RNA (CHEBI:33699)
carfentanyl (CHEBI:61084)
antiviral agent (CHEBI:22587)
Hepatitis (HP:0012115)
hepatitis (DOID:2237)
hepatitis B (DOID:2043)
hepatitis C (DOID:1883)
disease (EFO:0000408)
treatment (EFO:0000727)
HepG2 (EFO:0001187)
infectious disease (EFO:0005741)
hepatitis C infection (EFO:0003047)
control (EFO:0001461)
hepatitis B infection (EFO:0004197)
HuH-7 (EFO:0005384)
replicate (EFO:0000683)
dose (EFO:0000428)
enzyme linked immunosorbent assay (ELISA) (MMO:0000075)
death stage (UBERON:0000071)
life-death temporal boundary (UBERON:0035944)
integumental system (UBERON:0002416)
liver (UBERON:0002107)
anatomical system (UBERON:0000467)
execution phase of apoptosis (GO:0097194)

Gene List • 15105 Genes

Genes in threshold: 6751

Uploaded As Gene Symbol Homology Score Priority LinkOuts Emphasis  

Manage GeneSets

Analyze GeneSets

Manage Accounts

GeneWeaver Links

Policies


Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351

Application Version 1.5.13