{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:03:10Z","timestamp":1785420190299,"version":"3.56.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32400132"],"award-info":[{"award-number":["32400132"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"publisher","award":["2025A1515012441"],"award-info":[{"award-number":["2025A1515012441"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Open Research Project of the Key Laboratory of Viral Pathogenesis & Infection Prevention and Control of the Ministry of Education","award":["2024VPPC-R08"],"award-info":[{"award-number":["2024VPPC-R08"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,5,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Zika virus (ZIKV), belonging to the\n                      <jats:italic toggle=\"yes\">Flaviviridae<\/jats:italic>\n                      family, has been a severe threat to human health since the worldwide outbreak. ZIKV is capable of inducing fetal microcephaly, Guillain-Barr\u00e9 syndrome, and other serious neurological complications. Polypyrimidine tract-binding protein 1 (PTBP1) is a key member of the heterogeneous nuclear ribonucleoproteins (hnRNPs) family, functioning in selective mRNA splicing and gene expression regulation. Our previous study has indicated that the expression of PTBP1 increases in astrocytes upon ZIKV infection, yet the precise regulatory mechanisms underlying its role in viral replication remain elusive. In this study, we elucidated the specific pathway by which ZIKV upregulated PTBP1 expression through the activation of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) signal. Further investigation revealed that overexpression of PTBP1 effectively inhibited viral replication, whereas knockdown of PTBP1 significantly enhanced viral replication. Mechanistically, using co-immunoprecipitation assays for protein interaction screening, we identified an interaction between PTBP1 and ZIKV non-structural protein NS1. Detailed studies demonstrated that PTBP1 bound and colocalized with NS1 to lead to the degradation of NS1 protein via a lysosomal pathway. Collectively, our findings unveil a novel mechanism underlying that ZIKV infection induces the expression of PTBP1 via the HIF-1\u03b1 pathway. Subsequently, the accumulated PTBP1 binds to the ZIKV NS1 protein, promoting NS1 degradation and thereby effectively inhibiting viral replication. The study illustrates a distinct restricted cellular factor that regulates ZIKV replication, which provides a potential target for the control of viral replication and pathogenesis during the ZIKV epidemic.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Since the outbreak of ZIKV infection among humans in 2014, a Zika epidemic has caused Zika fever accompanied by fetal microcephaly, Guillain-Barr\u00e9 syndrome, and other neurological symptoms. Emerging evidence reveals that ZIKV infects astrocytes to specifically induce the expression of polypyrimidine tract-binding protein 1 (PTBP1), one of the hnRNP members. However, the interplay between PTBP1 and ZIKV replication is unclear. Here, we uncover a distinct manner that ZIKV induces PTBP1 expression through the activation of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) signal. Additionally, activation of the HIF-1\u03b1 signal hinders ZIKV replication, relying on PTBP1 accumulation. Further investigations suggest that PTBP1 restrains ZIKV replication by interacting with ZIKV NS1 protein, thereby leading to the degradation of NS1 protein via a lysosomal pathway. Collectively, our findings illustrate a novel restricted cellular factor PTBP1 mediated by HIF-1\u03b1 that regulates ZIKV replication, which provides a potential therapeutic target of viral replication and pathogenesis against the ZIKV pandemic.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01495-25","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T09:03:08Z","timestamp":1777280588000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["PTBP1 is upregulated in response to Zika virus infection and restrains viral replication by hijacking viral NS1 protein to induce NS1 degradation"],"prefix":"10.1128","volume":"100","author":[{"given":"Menglan","family":"Rao","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02xe5ns62","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Microbiology, 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