BibTex format
@article{Mechelli:2025:10.1073/pnas.2418783122,
author = {Mechelli, R and Umeton, R and Bellucci, G and Bigi, R and Rinaldi, V and Angelini, DF and Guerrera, G and Pignalosa, FC and Ilari, S and Patrone, M and Srinivasan, S and Cerono, G and Romano, S and Buscarinu, MC and Martire, S and Malucchi, S and Landi, D and Lorefice, L and Pizzolato, Umeton R and Anastasiadou, E and Trivedi, P and Fornasiero, A and Ferraldeschi, M and Di, Sapio A and Marfia, G and Cocco, E and Centonze, D and Uccelli, A and Di, Silvestre D and Mauri, P and de, Candia P and DAlfonso, S and Battistini, L and Farina, C and Magliozzi, R and Reynolds, R and Baranzini, SE and Matarese, G and Salvetti, M and Ristori, G and Alfredsson, L and Søndergaard, HB and Baranzini, SE and Barcellos, LF and Bernardinelli, L and Booth, D and Comabella, M and Compston, A and Cotsapas, C and DAlfonso, S and Dardiotis, E and De, Jager PL and Dubois, B and Esposito, F and Fontaine, B and Goris, A and Gourraud, P-A and Hadjigeorgiou, G and Hafler, DA and Haines, JL and Harbo, HF and Hauser, },
doi = {10.1073/pnas.2418783122},
journal = {Proceedings of the National Academy of Sciences},
title = {A disease-specific convergence of host and Epstein–Barr virus genetics in multiple sclerosis},
url = {http://dx.doi.org/10.1073/pnas.2418783122},
volume = {122},
year = {2025}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Recent sero-epidemiological studies have strengthened the hypothesis that Epstein–Barr virus (EBV) may be a causal factor in multiple sclerosis (MS). Given the complexity of the EBV–host interaction, various mechanisms may be responsible for the disease pathogenesis. Furthermore, it remains unclear whether this is a disease-specific process. Here, we showed that genes encoding EBV interactors are enriched in loci associated with MS but not with other diseases and in prioritized therapeutic targets. Analyses of MS blood and brain transcriptomes confirmed a dysregulation of MS-associated EBV interactors affecting the CD40 pathway. Such interactors were strongly enriched in binding sites for the EBV nuclear antigen 2 (EBNA2) viral transcriptional regulator, often in colocalization with CCCTC binding factor (CTCF) and RNA Polymerase II Subunit A (POLR2A). EBNA2 was expressed in the MS brain. The 1.2 EBNA2 allele downregulated the expression of the CD40 MS-associated gene analogously to the CD40 MS-risk variant. Finally, we showed that the 1.2 EBNA2 allele associates with the risk of MS. This study delineates how host and viral genetic variability converge in MS-specific pathogenetic mechanisms.
AU - Mechelli,R
AU - Umeton,R
AU - Bellucci,G
AU - Bigi,R
AU - Rinaldi,V
AU - Angelini,DF
AU - Guerrera,G
AU - Pignalosa,FC
AU - Ilari,S
AU - Patrone,M
AU - Srinivasan,S
AU - Cerono,G
AU - Romano,S
AU - Buscarinu,MC
AU - Martire,S
AU - Malucchi,S
AU - Landi,D
AU - Lorefice,L
AU - Pizzolato,Umeton R
AU - Anastasiadou,E
AU - Trivedi,P
AU - Fornasiero,A
AU - Ferraldeschi,M
AU - Di,Sapio A
AU - Marfia,G
AU - Cocco,E
AU - Centonze,D
AU - Uccelli,A
AU - Di,Silvestre D
AU - Mauri,P
AU - de,Candia P
AU - DAlfonso,S
AU - Battistini,L
AU - Farina,C
AU - Magliozzi,R
AU - Reynolds,R
AU - Baranzini,SE
AU - Matarese,G
AU - Salvetti,M
AU - Ristori,G
AU - Alfredsson,L
AU - Søndergaard,HB
AU - Baranzini,SE
AU - Barcellos,LF
AU - Bernardinelli,L
AU - Booth,D
AU - Comabella,M
AU - Compston,A
AU - Cotsapas,C
AU - DAlfonso,S
AU - Dardiotis,E
AU - De,Jager PL
AU - Dubois,B
AU - Esposito,F
AU - Fontaine,B
AU - Goris,A
AU - Gourraud,P-A
AU - Hadjigeorgiou,G
AU - Hafler,DA
AU - Haines,JL
AU - Harbo,HF
AU - Hauser,SL
AU - Hemmer,B
AU - Henry,R
AU - Hillert
AU - Hintzen,R
AU - Isobe,N
AU - Ivinson,AJ
AU - Kalra,S
AU - Khalil,M
AU - Kockum,I
AU - Lechner-Scott,J
AU - Martin,R
AU - Martinelli-Boneschi,F
AU - McCauley,JL
AU - McVean,G
AU - Oksenberg,JR
AU - Olsson,T
AU - Oturai,A
AU - Parnell,GP
AU - Patsopoulos,NA
AU - Pericak-Vance,MA
AU - Robertson,N
AU - Saarela,J
AU - Sawcer,SJ
AU - Smolders,J
AU - Stewart,GJ
AU - Taylor,B
AU - Yong,VW
AU - Zipp,F
AU - Barroso,I
AU - Blackwell,JM
AU - Bramon,E
AU - Brown,MA
AU - Casas,JP
AU - Caulfield,M
AU - Clayton,D
AU - Corvin,A
AU - Craddock,N
AU - Deloukas,P
AU - Donnelly,P
AU - Duncanson,A
AU - Farrall,M
AU - Hall,A
AU - Hattersley,A
AU - Jankowski,J
AU - Markus,HS
AU - Mathew,CG
AU - McCarthy,M
AU - Palmer,CNA
AU - Parkes,M
AU - Plomin,R
AU - Rautanen,A
AU - Samani,N
AU - Sawcer,S
AU - Todd,J
AU - Trembath,RC
AU - Viswanathan,AC
AU - Wood,NW
AU - Worthington,J
AU - Spencer,CCA
AU - Band,G
AU - Bellenguez,C
AU - Freeman,C
AU - Hellenthal,G
AU - Giannoulatou,E
AU - Pirinen,M
AU - Pearson,R
AU - Strange,A
AU - Su,Z
AU - Vukcevic,D
AU - Langford,C
AU - Hunt,SE
AU - Edkins,S
AU - Gwilliam,R
AU - Blackburn,H
AU - Bumpstead,SJ
AU - Dronov,S
AU - Gillman,M
AU - Gray,E
AU - Hammond,N
AU - Jayakumar,A
AU - McCann,OT
AU - Liddle,J
AU - Potter,SC
AU - Ravindrarajah,R
AU - Ricketts,M
AU - Waller,MJ
AU - Weston,P
AU - Widaa,S
AU - Whittaker,P
AU - Dilthey,A
AU - Leslie,S
AU - Moutsianas,L
AU - Perez,ML
AU - McVean,G
DO - 10.1073/pnas.2418783122
PY - 2025///
SN - 0027-8424
TI - A disease-specific convergence of host and Epstein–Barr virus genetics in multiple sclerosis
T2 - Proceedings of the National Academy of Sciences
UR - http://dx.doi.org/10.1073/pnas.2418783122
UR - https://doi.org/10.1073/pnas.2418783122
VL - 122
ER -