Evidence map›Paper›PMID 41516315›Full record

ArticleInternational journal of molecular sciences2025

EBV Early Lytic Antigens, EBNA2 and PDL-1, in Progressive Multiple Sclerosis Brain: A Coordinated Contribution to Viral Immune Evasion.

Lucia Benincasa, Barbara Rosicarelli, Chiara Meloni, Barbara Serafini

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. 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
–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

1 citing paper in PubMed.

  1. 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

4 authors.

Lucia BenincasaDepartment of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.ORCID 0009-0009-8482-8334
Barbara RosicarelliDepartment of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.ORCID 0000-0002-9945-1527
Chiara MeloniDepartment of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.ORCID 0009-0005-9897-080X
Barbara SerafiniDepartment of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.ORCID 0000-0002-6853-1161

Funding

Associazione Italiana Sclerosi Multipla 2022/R-Single/006European Union 101137235
6 · The paper itself

Abstract

Epstein-Barr virus (EBV) infection shows the strongest causative association with multiple sclerosis (MS), but its contribution to disease progression and the mechanisms allowing for viral persistence in the MS brain are still elusive. Studies in post-mortem MS brain tissue indicate an ongoing yet ineffective antiviral immune reaction in advanced stages of the disease. EBV has evolved strategies to evade immune recognition and clearance by the host immune system during both the latency and lytic phase of its life cycle. Recent evidence demonstrates that cells expressing EBV latent membrane protein (LMP) 2A exploit the PD-1/PDL1 inhibitory immune checkpoint to escape immune surveillance and maintain a persistent latent infection in the MS brain. This study investigated whether the virus also utilizes this inhibitory mechanism during other phases of the viral life cycle. By using multiple immunostainings on highly inflamed MS brain tissues containing meningeal tertiary lymphoid structures (TLSs), we analyzed PD-L1 expression on EBV-infected cells expressing EBNA2, five EBV lytic gene products, BZLF1, BHRF1, BMRF1, BALF2, and gp350/220, as well as on follicular dendritic cells within the TLSs. This is the first study describing in secondary progressive MS brain tissue the expression and the cellular and tissue distribution of PD-L1 on EBV-infected cells being in different stages of the viral life cycle, and confirms the meningeal TLSs as immune-permissive habitats favoring the maintenance of an intracerebral EBV reservoir.

Indexed as

B7-H1 AntigenBrainEpstein-Barr Virus InfectionsEpstein-Barr Virus Nuclear AntigensImmune EvasionMultiple SclerosisViral ProteinsAdultAged, 80 and overB-LymphocytesCD4-Positive T-LymphocytesDisease ProgressionHerpesvirus 4, HumanHumansMiddle AgedB7-H1 AntigenCD274 protein, humanEBNA-2 protein, Human herpesvirus 4Epstein-Barr Virus Nuclear AntigensViral ProteinsEpstein-Barr virusinhibitory immune checkpointmultiple sclerosistertiary lymphoid organs

Identifiers

PMID41516315
PMCPMC12785848

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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.