Evidence mapPaperPMID 37547182Full record

ArticleJournal of extracellular biology2023

Retroviral b-Zip protein (HBZ) contributes to the release of soluble and exosomal immune checkpoint molecules in the context of neuroinflammation.

Julie Joseph, Thomas A Premeaux, Daniel O Pinto, Abhishek Rao, Shrobona Guha, Amanda R Panfil, Alison J Carey, Lishomwa C Ndhlovu, Elke S Bergmann-Leitner, Pooja Jain

Erratum issuedOpen access · diamondAbstract read
In one paragraph

Article in Journal of extracellular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-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

6 citing papers in PubMed, 5 citations in OpenAlex.

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  4. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 1 country.

Julie JosephDepartment of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, PA.
Thomas A PremeauxWeill Cornel Medicine Department of Medicine, Division of Infectious Diseases, New York, NY.
Daniel O PintoImmunology Core, Biologics Research and Development, Walter Reed Army Institute of Research, Silver Springs, MD.
Abhishek RaoDepartment of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, PA.
Shrobona GuhaDepartment of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA.
Amanda R PanfilThe Ohio State University, College of Veterinary Medicine, Center for Retrovirus Research, Columbus, Ohio, USA.
Alison J CareyDepartment of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, PA.
Lishomwa C NdhlovuWeill Cornel Medicine Department of Medicine, Division of Infectious Diseases, New York, NY.
Elke S Bergmann-LeitnerImmunology Core, Biologics Research and Development, Walter Reed Army Institute of Research, Silver Springs, MD.
Pooja JainDepartment of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, PA.
Drexel University · USCornell College · USOak Ridge Associated Universities · USThe Ohio State University · USWalter Reed Army Institute of Research · US

Funding

Retrovirus Models of Lymphocyte Transformation/DiseaseP01CA100730 · WASHINGTON UNIVERSITY · 2003 to 2025
$7.8M
Pre-clinical testing of a novel immunotherapy for HTLV-induced neurologic diseaseR01NS097147 · NINDS · DREXEL UNIVERSITY · PI Pooja Jain · 2021 to 2021
$431k
Interdisciplinary And Translational Research Training In NeurohivT32MH079785 · TEMPLE UNIV OF THE COMMONWEALTH · 2025 to 2025
$57k
NCI NIH HHS P01 CA100730NIMH NIH HHS T32 MH079785NINDS NIH HHS R01 NS097147
6 · The paper itself

Abstract

HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive, neuroinflammatory demyelinating condition of the spinal cord. We have previously shown that aberrant expression and activity of immune checkpoint (ICP) molecules such as PD-1 and PD-L1/PD-L2, negatively associates with the cytolytic potential of T cells in individuals with HAM/TSP. Interestingly, ICPs can exist in a soluble cell-free form and can be carried on extracellular vesicles (EVs) and exosomes (small EVs, <300nm) while maintaining their immunomodulatory activity. Therefore, we investigated the role of soluble and exosomal ICPs in HTLV-1 associated neuroinflammation. For the very first time, we demonstrate a unique elevated presence of several stimulatory (CD27, CD28, 4-1BB) and inhibitory (BTLA, CTLA-4, LAG-3, PD-1, PD-L2) ICP receptors in HAM/TSP sera, and in purified exosomes from a HAM/TSP-derived HTLV-1-producing (OSP2) cells. These ICPs were found to be co-localized with the endosomal sorting complex required for transport (ESCRT) pathway proteins and exhibited functional binding with their respective ligands. Viral proteins and cytokines (primarily IFNγ) were found to be present in purified exosomes. IFNγ exposure enhanced the release of ICP molecules while antiretroviral drugs (Azidothymidine and Lopinavir) significantly inhibited this process. HTLV-1 b-Zip protein (HBZ) has been linked to factors that enhance EV release and concurrent knockdown here led to the reduced expression of ESCRT associated genes (

Indexed as

BTLAHAM/TSPHTLV-1Immune CheckpointsPD-1PD-L1/2

Identifiers

PMID37547182
PMCPMC10399615
OpenAlexW4384563854

What Socratic holds

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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 Socratic graph.