{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T01:53:17Z","timestamp":1793757197929,"version":"4.6.1"},"reference-count":66,"publisher":"National Academy of Sciences","issue":"41","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds for the Central Universities, Sun Yat-sen University","award":["22hytd05"],"award-info":[{"award-number":["22hytd05"]}]},{"name":"Major Project of Guangzhou National Laboratory","award":["GZNL2024A01017"],"award-info":[{"award-number":["GZNL2024A01017"]}],"id":[{"id":"https:\/\/ror.org\/03ybmxt82","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,10,14]]},"abstract":"<jats:p>\n                    The small interfering RNA (siRNA) pathway is a highly conserved antiviral defense mechanism in vertebrates and invertebrates. Although the core components of this pathway are well characterized, its upstream regulatory networks remain poorly understood. Here, we identify the integrated stress response (ISR) as a negative regulator of the siRNA pathway, and demonstrate that the picorna-like virus CrPV (Cricket Paralysis Virus) exploits this mechanism for immune evasion. Mechanistically, the picorna-like virus triggers the ISR through transcriptional suppression of\n                    <jats:italic toggle=\"yes\">ppp1r15<\/jats:italic>\n                    , a key regulator of eukaryotic initiation factor 2\u03b1 (eIF2\u03b1) dephosphorylation. ISR activation subsequently induces the autophagy-lysosomal pathway by up-regulating\n                    <jats:italic toggle=\"yes\">Atg1<\/jats:italic>\n                    transcription in an ATF4-dependent manner. This process leads to selective degradation of Argonaute 2 (Ago2) and other core components of the RNA-induced silencing complex (RISC), thereby suppressing the host RNA interference (RNAi) machinery and enhancing viral replication. Our findings uncover an unconventional immune evasion strategy employed by a picorna-like virus and establish a previously unrecognized crosstalk between the ISR and siRNA pathways.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2511857122","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:21:19Z","timestamp":1759940479000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":7,"title":["The integrated stress response suppresses antiviral RNA interference by autophagy-mediated degradation of the RNA-induced silencing complex"],"prefix":"10.1073","volume":"122","author":[{"given":"Qiyu","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Ecology, Sun Yat-sen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyue","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Ecology, Sun Yat-sen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5841-5977","authenticated-orcid":false,"given":"Jiayin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Ecology, Sun Yat-sen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Ecology, Sun Yat-sen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixian","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Ecology, Sun Yat-sen University","place":["Shenzhen, 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Wang The integrated stress response suppresses antiviral RNA interference by autophagy-mediated degradation of RNA-induced silencing complex. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE309081. Deposited 24 September 2025."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2511857122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:22:03Z","timestamp":1759940523000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2511857122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,8]]},"references-count":66,"journal-issue":{"issue":"41","published-print":{"date-parts":[[2025,10,14]]}},"alternative-id":["10.1073\/pnas.2511857122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2511857122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,8]]},"assertion":[{"value":"2025-05-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2511857122"}}