{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:52:24Z","timestamp":1786121544764,"version":"build-2736575974"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"publisher","award":["2023GXNSFBA026170"],"award-info":[{"award-number":["2023GXNSFBA026170"]}],"id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"publisher","award":["2023GXNSFBA026080"],"award-info":[{"award-number":["2023GXNSFBA026080"]}],"id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes severe encephalitis in humans and reproductive disorders in pigs. However, the host factors that regulate JEV infection and replication remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>In this study, we used porcine kidney cells (PK15) infected with the attenuated JEV strain SA14-14-2 to identify host proteins interacting with the JEV envelope (E) protein by immunoprecipitation coupled with LC-MS\/MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Annexin A2 (ANXA2) was identified as a candidate host factor associated with JEV infection. ANXA2 expression was increased during JEV infection, and co- immunoprecipitation confirmed its association with the JEV E protein. Inhibition of ANXA2 with antibody reduced JEV RNA replication in a dose-dependent manner. To further define its function, ANXA2 knockout (KO) PK15 cells were generated using CRISPR\/Cas9. Compared with wild-type cells, ANXA2-KO cells showed significantly reduced viral RNA accumulation, especially during the early stage of JEV infection (2-6hpi), when the viral entry and initiates replication, lower JEV E protein expression, and decreased progeny virus titers. In addition, ANXA2 deficiency altered the expression of clathrin-mediated endocytosis- related genes and proteins, including CLTC, CLTB, AP2M1, and EPS15, and affected Akt phosphorylation during early infection. Fluorescence recovery after photobleaching analysis (FRAP) of DiD-labeled JEV particles indicated impaired intracellular transport in ANXA2-KO cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>these findings identify ANXA2 as a host factor that promotes JEV infection and replication, at least in part by regulating clathrin-mediated endocytosis and intracellular transport. ANXA2 may represent a potential target for future antiviral strategies against JEV.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1858383","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:29:15Z","timestamp":1786080555000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Annexin A2 facilitates Japanese encephalitis virus replication by regulating endocytosis and intracellular transport in PK15 cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Longqin","family":"Wei","sequence":"first","affiliation":[{"name":"School of Laboratory Medicine and Biotechnology, Guilin Medical University","place":["Guilin, Guangxi, China"]},{"name":"Research Service Department, Guilin People's Hospital","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saixiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Guilin Medical University","place":["Guilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine and Biotechnology, Guilin Medical University","place":["Guilin, Guangxi, China"]},{"name":"Research Service Department, Guilin People's Hospital","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine and Biotechnology, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Luo","sequence":"additional","affiliation":[{"name":"Scientific Research Center, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Li","sequence":"additional","affiliation":[{"name":"Guilin Animal Disease Prevention and Control Center","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanzhen","family":"Huang","sequence":"additional","affiliation":[{"name":"Scientific Research Center, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xishi","family":"Huang","sequence":"additional","affiliation":[{"name":"Scientific Research Center, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lantao","family":"Gu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Multimodal Biomarkers and Precision Diagnosis, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingli","family":"Fang","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine and Biotechnology, Guilin Medical University","place":["Guilin, Guangxi, China"]},{"name":"Scientific Research Center, Guilin Medical University","place":["Guilin, Guangxi, China"]},{"name":"Guangxi Key Laboratory of Multimodal Biomarkers and Precision Diagnosis, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.3390\/ijms20092336","article-title":"Flavivirus replication organelle biogenesis in the endoplasmic reticulum: comparison with other single-stranded positive-sense RNA viruses","volume":"20","author":"Arakawa","year":"2019","journal-title":"Int. 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