Evidence map›Paper›PMID 39605359›Full record

ArticlebioRxiv : the preprint server for biology2024

Identification of TAP2 protein variants resistant to inhibition by the HSV1 ICP47 protein.

Gregory Nagy, Rebecca Presley, Shruti Dhar, Hyeongseon Jeon, Lynn Moreira, Olivia Tull, Arkobrato Gupta, Dongjun Chung, Philip N Tsichlis, Jeffrey D Parvin

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Gregory NagyDepartment of Biomedical Informatics and the OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
Rebecca PresleyDepartment of Biomedical Informatics and the OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
Shruti DharDepartment of Biomedical Informatics and the OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
Hyeongseon JeonDepartment of Biomedical Informatics and the OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
Lynn MoreiraDepartment of Biomedical Informatics and the OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
Olivia TullDepartment of Biomedical Informatics and the OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
Arkobrato GuptaDepartment of Biomedical Informatics and the OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
Dongjun ChungDepartment of Biomedical Informatics and the OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
Philip N TsichlisDepartment of Cancer Biology & Genetics and the OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
Jeffrey D ParvinDepartment of Biomedical Informatics and the OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH.ORCID 0000-0001-5616-1928

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
Multiplexed functional analysis of BRCA1and BARD1 missense variants in DNA repairR01CA228083 · NCI · OHIO STATE UNIVERSITY · PI PARVIN, JEFFREY D · 2019 to 2023
$2.4M
Integrative Training in Biomedical SystemsT32GM068412 · NIGMS · OHIO STATE UNIVERSITY · PI PARVIN, JEFFREY D · 2005 to 2020
$2.4M
NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA228083NIGMS NIH HHS T32 GM068412
6 · The paper itself

Abstract

Herpes Simplex Virus 1 evades the host immune system by expressing a protein, ICP47, that binds to and inhibits the heterodimeric Transporter Associated with Antigen Processing (TAP). We screened a library of 1786 variants in TAP2, one of the components of the TAP heterodimer, and identified 39 variants that were resistant to inhibition by ICP47. Of these 39 variants, five were individually tested, and three (T257I, S274H, and T244R) were confirmed to be significantly resistant to inhibition by ICP47. This resistance to inhibition did not extend to the Epstein Barr Virus BNLF2a protein, another viral factor known to inhibit antigen presentation by targeting TAP. These three residues localize close to the binding site of ICP47, on the 3D structure of TAP, but only Ser274 is spatially close to the antigenic peptide binding site of TAP. These results functionally resolve the TAP2 residues required for peptide binding from those required for ICP47 binding and identify TAP2 residues whose targeting with small molecule inhibitors could effectively prevent Herpes virus downregulation of antigen processing.

Indexed as

Antigen presentationHerpes Simplex Virus 1ICP47immune evasionMajor Histocompatibility Complex class ITransporter Associated with Antigen Processing

Identifiers

PMID39605359
PMCPMC11601387

What OpenQuestion holds

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Registered trials

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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.