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However, the broader impact of cbVGs on the functional states of host cells remains undefined. Here, we developed a single-cell RNA-sequencing and computational framework to map cbVG-driven host responses during Sendai virus infection. Unsupervised profiling identified distinct transcriptional states throughout the course of infection, highlighting a shift from early antiviral signaling to later inflammatory and remodeling programs. Stratifying infected cells by cbVG status demonstrated that cbVG-positive cells initiate interferon and chemokine programs, which later spread to cbVG-negative cells. At later stages, cbVG-positive cells acquire additional signaling, cytoskeletal, transcriptional, and stress-adaptation programs, which are absent in cbVG-clean infection. This work defines the broader cbVG-driven layered and dynamic host response and provides a valuable high-resolution resource of the temporal cellular response to a virus infection.<\/jats:p>","DOI":"10.1371\/journal.ppat.1014184","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T17:43:19Z","timestamp":1777311799000},"page":"e1014184","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Detailed single-cell mapping of the transcriptional response to a virus infection driven by copy-back viral genomes"],"prefix":"10.1371","volume":"22","author":[{"given":"Yanling","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emna","family":"Achouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munyaradzi","family":"Tambo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7669-6572","authenticated-orcid":true,"given":"Carolina B.","family":"L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"issue":"3","key":"ppat.1014184.ref001","doi-asserted-by":"crossref","DOI":"10.1128\/mmbr.00086-21","article-title":"A virus is a community: diversity within negative-sense RNA virus populations","volume":"86","author":"LJ Gonz\u00e1lez 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