Evidence map›Paper›PMID 33852610›Full record

ArticlePloS one2021

The synthetic opioid fentanyl enhances viral replication in vitro.

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

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.9field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Illicit Fentanyl Use and Hepatitis C Virus Seroconversion Among People Who Inject Drugs in Tijuana and San Diego: Results From a Binational Cohort Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Ling KongDivision of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
Rebekah KarnsDigestive Health Center, Cincinnati Children's Hospital, Cincinnati, OH, United States of America.
Mohamed Tarek M ShataDivision of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
Jennifer L BrownAddiction Sciences Division, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
Michael S LyonsCenter for Addiction Research, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
Kenneth E ShermanDivision of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
Jason T BlackardDivision of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.ORCID 0000-0003-2876-3811
University of Cincinnati Medical Center · USCincinnati Children's Hospital Medical Center · US

Funding

Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4M
Omics analysis of HIV during synthetic opioid exposureR61DA048439 · NIDA · UNIVERSITY OF CINCINNATI · PI BLACKARD, JASON T · 2019 to 2021
$2.1M
Genotypic& phenotypic characterization of the HCV polymerase (NS5B) in HIVR01GM105414 · NIGMS · UNIVERSITY OF CINCINNATI · PI BLACKARD, JASON T · 2013 to 2017
$1.5M
Omics analysis of HIV during synthetic opioid exposureR33DA048439 · NIDA · UNIVERSITY OF CINCINNATI · PI BLACKARD, JASON T · 2022 to 2023
$1.2M
NIDA NIH HHS R33 DA048439NIDA NIH HHS R61 DA048439NIDDK NIH HHS P30 DK078392NIGMS NIH HHS R01 GM105414
6 · The paper itself

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.

Indexed as

Virus ReplicationAnalgesics, OpioidApoptosisCytopathogenic Effect, ViralFentanylHepacivirusHepatitis BHepatitis B virusHepatitis CHepatocytesHep G2 CellsHumansIn Vitro TechniquesTranscriptomeAnalgesics, OpioidFentanyl

Identifiers

PMID33852610
PMCPMC8046189
OpenAlexW3156622707

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.