Evidence map›Paper›PMID 37436080›Full record

ArticlemBio2023

Hepatitis delta virus RNA decline post-inoculation in human NTCP transgenic mice is biphasic.

Stephanie Maya, Leeor Hershkovich, E Fabian Cardozo-Ojeda, Elham Shirvani-Dastgerdi, Jay Srinivas, Louis Shekhtman, Susan L Uprichard, Andrew R Berneshawi, Thomas R Cafiero, Harel Dahari and 1 more

Open access · goldAbstract read
In one paragraph

Article in mBio, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 43% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Stephanie Maya *Department of Molecular Biology, Princeton University , Princeton, New Jersey, USA.ORCID 0000-0001-7321-9706
Leeor Hershkovich *Department of Medicine, The Program for Experimental & Theoretical Modeling, Division of Hepatology, Stritch School of Medicine, Loyola University Chicago , Maywood, Illinois, USA.ORCID 0000-0001-7361-4765
E Fabian Cardozo-Ojeda *Department of Medicine, The Program for Experimental & Theoretical Modeling, Division of Hepatology, Stritch School of Medicine, Loyola University Chicago , Maywood, Illinois, USA.ORCID 0000-0001-8690-9896
Elham Shirvani-DastgerdiDepartment of Molecular Biology, Princeton University , Princeton, New Jersey, USA.
Jay SrinivasDepartment of Medicine, The Program for Experimental & Theoretical Modeling, Division of Hepatology, Stritch School of Medicine, Loyola University Chicago , Maywood, Illinois, USA.
Louis ShekhtmanDepartment of Medicine, The Program for Experimental & Theoretical Modeling, Division of Hepatology, Stritch School of Medicine, Loyola University Chicago , Maywood, Illinois, USA.ORCID 0000-0001-5273-8363
Susan L UprichardDepartment of Medicine, The Program for Experimental & Theoretical Modeling, Division of Hepatology, Stritch School of Medicine, Loyola University Chicago , Maywood, Illinois, USA.ORCID 0000-0001-5691-1557
Andrew R BerneshawiDepartment of Molecular Biology, Princeton University , Princeton, New Jersey, USA.
Thomas R CafieroDepartment of Molecular Biology, Princeton University , Princeton, New Jersey, USA.
Harel DahariDepartment of Medicine, The Program for Experimental & Theoretical Modeling, Division of Hepatology, Stritch School of Medicine, Loyola University Chicago , Maywood, Illinois, USA.ORCID 0000-0002-3357-1817
Alexander PlossDepartment of Molecular Biology, Princeton University , Princeton, New Jersey, USA.ORCID 0000-0001-9322-7252
Loyola University Chicago · USPrinceton University · US

Funding

Data-Driven Mathematical and Computational Modeling of Hepatitis D Infection and Treatment ResponseR01AI146917 · NIAID · LOYOLA UNIVERSITY CHICAGO · PI DAHARI, HAREL · 2020 to 2024
$3.5M
Mechanisms of hepatitis B virus cccDNA formationR01AI153236 · NIAID · PRINCETON UNIVERSITY · PI PLOSS, ALEXANDER · 2020 to 2024
$2.8M
Collaborative Integration of Hepatitis B Molecular Virology and Mathematical/Computational ModelingR01AI144112 · NIAID · LOYOLA UNIVERSITY CHICAGO · PI DAHARI, HAREL, UPRICHARD, SUSAN L. · 2019 to 2023
$2.2M
NIAID NIH HHS R01 AI144112NIAID NIH HHS R01 AI146917NIAID NIH HHS R01 AI153236
6 · The paper itself

Abstract

Chronic infection with hepatitis B and delta viruses (HDV) is the most serious form of viral hepatitis due to more severe manifestations of an accelerated progression to liver fibrosis, cirrhosis, and hepatocellular carcinoma. We characterized early HDV kinetics post-inoculation and incorporated mathematical modeling to provide insights into host-HDV dynamics. We analyzed HDV RNA serum viremia in 192 immunocompetent (C57BL/6) and immunodeficient (NRG) mice that did or did not transgenically express the HDV receptor-human sodium taurocholate co-transporting polypeptide (hNTCP). Kinetic analysis indicates an unanticipated biphasic decline consisting of a sharp first-phase and slower second-phase decline regardless of immunocompetence. HDV decline after re-inoculation again followed a biphasic decline; however, a steeper second-phase HDV decline was observed in NRG-hNTCP mice compared to NRG mice. HDV-entry inhibitor bulevirtide administration and HDV re-inoculation indicated that viral entry and receptor saturation are not major contributors to clearance, respectively. The biphasic kinetics can be mathematically modeled by assuming the existence of a non-specific-binding compartment with a constant on/off-rate and the steeper second-phase decline by a loss of bound virus that cannot be returned as free virus to circulation. The model predicts that free HDV is cleared with a half-life of 35 minutes (standard error, SE: 6.3), binds to non-specific cells with a rate of 0.05 per hour (SE: 0.01), and returns as free virus with a rate of 0.11 per hour (SE: 0.02). Characterizing early HDV-host kinetics elucidates how quickly HDV is either cleared or bound depending on the immunological background and hNTCP presence. IMPORTANCE The persistence phase of HDV infection has been studied in some animal models; however, the early kinetics of HDV

Indexed as

Hepatitis Delta VirusLiver NeoplasmsAnimalsHumansKineticsMiceMice, Inbred C57BLMice, TransgenicRNARNAanimal modelhepatitis B virushepatitis delta virusmathematical modelingviral hepatitis

Identifiers

PMID37436080
PMCPMC10470517
OpenAlexW4383999214

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.