{"doi":"10.1002/jmv.28957","title":"NAC1 confines virus‐specific memory formation of CD4<sup>+</sup> T cells through the ROCK1‐mediated pathway","abstract":"Abstract Nucleus accumbens‐associated protein 1 (NAC1), a transcriptional cofactor, has been found to play important roles in regulating regulatory T cells, CD8 + T cells, and antitumor immunity, but little is known about its effects on T‐cell memory. In this study, we found that NAC1 expression restricts memory formation of CD4 + T cells during viral infection. Analysis of CD4 + T cells from wild‐type (WT) and NAC1‐deficient ( −/− ) mice showed that NAC1 is essential for T‐cell metabolism, including glycolysis and oxidative phosphorylation, and supports CD4 + T‐cell survival in vitro. We further demonstrated that a deficiency of NAC1 downregulates glycolysis and correlates with the AMPK‐mTOR pathway and causes autophagy defective in CD4 + T cells. Loss of NAC1 reduced the expression of ROCK1 and the phosphorylation and stabilization of BECLIN1. However, a forced expression of ROCK1 in NAC1 −/− CD4 + T cells restored autophagy and the activity of the AMPK‐mTOR pathway. In animal experiments, adoptively transferred NAC1 −/− CD4 + T cells or NAC1 −/− mice challenged with VACV showed enhanced formation of VACV‐specific CD4 + memory T cells compared to adoptively transferred WT CD4 + T cells or WT mice. This memory T‐cell formation enhancement was abrogated by forcing expression of ROCK1. Our study reveals a novel role for NAC1 as a suppressor of CD4 + T‐cell memory formation and suggests that targeting NAC1 could be a new approach to promoting memory CD4 + T‐cell development, which is critical for an effective immune response against pathogens.","journal":"Journal of Medical Virology","year":2023,"id":364231,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9603,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":486872,"name":"Hao‐Yun Peng","orcid":"0000-0001-5151-590X","position":1,"is_corresponding":false},{"id":486870,"name":"Jugal Kishore Das","orcid":"0000-0002-4553-2196","position":2,"is_corresponding":false},{"id":486871,"name":"Anil Kumar","orcid":"0000-0002-7611-5918","position":3,"is_corresponding":false},{"id":486873,"name":"Yijie Ren","orcid":"0000-0002-5753-421X","position":4,"is_corresponding":false},{"id":630571,"name":"Darby J. Ballard","orcid":"0000-0001-5766-851X","position":5,"is_corresponding":false},{"id":486874,"name":"Xiaofang Xiong","orcid":"0000-0001-8276-4415","position":6,"is_corresponding":false},{"id":835939,"name":"Wen Yang","orcid":"0000-0002-2032-1982","position":7,"is_corresponding":false},{"id":517659,"name":"Xingcong Ren","orcid":"0000-0003-4430-2935","position":8,"is_corresponding":false},{"id":442347,"name":"Paul de Figueiredo","orcid":"0000-0002-3878-5064","position":9,"is_corresponding":false},{"id":351216,"name":"Jinming Yang","orcid":"0000-0002-8703-0493","position":10,"is_corresponding":false},{"id":486875,"name":"Jianxun Song","orcid":"0000-0002-9734-6176","position":11,"is_corresponding":false},{"id":486869,"name":"Liqing Wang","orcid":"0009-0000-9896-3793","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T01:14:36.728255Z","pmid":"37465969","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}