PMID- 37310118 OWN - NLM STAT- MEDLINE DCOM- 20230615 LR - 20230625 IS - 1096-9071 (Electronic) IS - 0146-6615 (Linking) VI - 95 IP - 6 DP - 2023 Jun TI - Peptidome-wide association analysis of Epstein-Barr virus identifies epitope repertoires associated with nasopharyngeal carcinoma. PG - e28860 LID - 10.1002/jmv.28860 [doi] AB - Human leukocyte antigen (HLA) molecules are essential for presenting Epstein-Barr virus (EBV) antigens and are closely related to nasopharyngeal carcinoma (NPC). This study aims to systematically investigate the association between HLA-bound EBV peptides and NPC risk through in silico HLA-peptide binding prediction. A total of 455 NPC patients and 463 healthy individuals in NPC endemic areas were recruited, and HLA-target sequencing was performed. HLA-peptide binding prediction for EBV, followed by peptidome-wide logistic regression and motif analysis, was applied. Binding affinity changes for EBV peptides carrying high-risk mutations were analyzed. We found that NPC-associated EBV peptides were significantly enriched in immunogenic proteins and core linkage disequilibrium (LD) proteins related to evolution, especially those binding HLA-A alleles (p = 3.10 x 10(-4) for immunogenic proteins and p = 8.10 x 10(-5) for core LD proteins related to evolution). These peptides were clustered and showed binding motifs of HLA supertypes, among which supertype A02 presented an NPC-risk effect (p(adj) = 3.77 x 10(-4) ) and supertype A03 presented an NPC-protective effect (p(adj) = 4.89 x 10(-4) ). Moreover, a decreased binding affinity toward risk HLA supertype A02 was observed for the peptide carrying the NPC-risk mutation BNRF1 V1222I (p = 0.0078), and an increased binding affinity toward protective HLA supertype A03 was observed for the peptide carrying the NPC-risk mutation BALF2 I613V (p = 0.022). This study revealed the distinct preference of EBV peptides for binding HLA supertypes, which may contribute to shaping EBV population structure and be involved in NPC development. CI - (c) 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. FAU - Deng, Chang-Mi AU - Deng CM AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Wang, Tong-Min AU - Wang TM AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - He, Yong-Qiao AU - He YQ AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Zhang, Wen-Li AU - Zhang WL AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Xue, Wen-Qiong AU - Xue WQ AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Li, Dan-Hua AU - Li DH AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Yang, Da-Wei AU - Yang DW AD - School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China. FAU - Wang, Qiao-Ling AU - Wang QL AD - School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China. FAU - Liao, Ying AU - Liao Y AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Diao, Hua AU - Diao H AD - School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China. FAU - Jiang, Cheng-Tao AU - Jiang CT AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Zhang, Jiang-Bo AU - Zhang JB AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Yuan, Lei-Lei AU - Yuan LL AD - School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China. FAU - Chen, Xue-Yin AU - Chen XY AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Zhou, Ting AU - Zhou T AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Li, Xi-Zhao AU - Li XZ AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Zhang, Pei-Fen AU - Zhang PF AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Zheng, Xiao-Hui AU - Zheng XH AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Zhang, Shao-Dan AU - Zhang SD AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Hu, Ye-Zhu AU - Hu YZ AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Xu, Miao AU - Xu M AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Zeng, Mu-Sheng AU - Zeng MS AUID- ORCID: 0000-0003-3509-5591 AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Feng, Lin AU - Feng L AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Jia, Wei-Hua AU - Jia WH AUID- ORCID: 0000-0002-0528-8715 AD - State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. AD - School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Med Virol JT - Journal of medical virology JID - 7705876 RN - 0 (Epitopes) RN - 0 (Histocompatibility Antigens Class II) SB - IM MH - Humans MH - Epitopes MH - Herpesvirus 4, Human/genetics MH - *Epstein-Barr Virus Infections/complications/genetics MH - Nasopharyngeal Carcinoma/genetics MH - Histocompatibility Antigens Class II MH - *Nasopharyngeal Neoplasms/genetics OTO - NOTNLM OT - Epstein-Barr virus OT - human leukocyte antigen OT - nasopharyngeal carcinoma OT - peptide-binding motif OT - peptidome-wide association EDAT- 2023/06/13 13:12 MHDA- 2023/06/15 06:41 CRDT- 2023/06/13 09:03 PHST- 2023/05/29 00:00 [revised] PHST- 2023/02/25 00:00 [received] PHST- 2023/05/30 00:00 [accepted] PHST- 2023/06/15 06:41 [medline] PHST- 2023/06/13 13:12 [pubmed] PHST- 2023/06/13 09:03 [entrez] AID - 10.1002/jmv.28860 [doi] PST - ppublish SO - J Med Virol. 2023 Jun;95(6):e28860. doi: 10.1002/jmv.28860.