{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T23:45:43Z","timestamp":1791762343414,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100023692","name":"Doherty Institute","doi-asserted-by":"publisher","award":["CGCPT00022"],"award-info":[{"award-number":["CGCPT00022"]}],"id":[{"id":"10.13039\/501100023692","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunol Cell Biol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Here, we assessed whether spatially resolved capture of polyadenylated mRNA permitted simultaneous screening of host and viral responses in\u00a0situ. Fresh\u2010frozen lung samples from mice infected with H1N1 influenza A strain, PR8, were processed via genome\u2010wide, spatial transcriptomics (ST) at 10\u2010\u03bcm resolution. To determine if specific cell\u2010types were detectable within the ST data, we first performed cellular deconvolution using publicly available, single\u2010cell RNA\u2010seq data of immune and non\u2010immune cells from PR8\u2010infected lungs. This revealed expected structures such as rings of epithelial cells lining airways, and at Day 10 post\u2010infection (p.i.) unexpected structures dominated by B cells. We next screened ST data alone for groups of genes displaying similar spatial expression patterns. This again identified at Day 10 p.i. cellular aggregates enriched for genes associated with B cell biology. Mapping these gene signatures to a B cell transcriptomic atlas suggested plasmablasts had emerged early in the lung, which was confirmed by flow cytometry. Finally, by mapping ST data to the influenza A genome, we observed widespread expression of all 10 viral transcripts across samples at Day 4 but not Day 10 p.i., consistent with viral clearance. Cellular deconvolution analysis at Day 4 p.i. revealed proportions of every detected cell\u2010type harbored viral transcripts, suggesting indiscriminate infection across the specific area of tissue examined. Subsequent whole\u2010section immunohistochemical assessment further supported the phenomenon of localized indiscriminate infection, with these areas found adjacent to minimally infected zones. Thus, spatial screening of mRNA in tissues can simultaneously inform upon viral pathogenesis and host responses to infection.<\/jats:p>","DOI":"10.1111\/imcb.70170","type":"journal-article","created":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T23:30:56Z","timestamp":1791761456000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Host\u2013Pathogen Screening of the Lung During Severe Influenza Using Spatial Transcriptomics"],"prefix":"10.1111","author":[{"given":"Marcus Z. W.","family":"Tong","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology University of Melbourne, Located at the Peter Doherty Institute for Infection and Immunity  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0898-4131","authenticated-orcid":false,"given":"Oliver P.","family":"Skinner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Melbourne, Located at the Peter Doherty Institute for Infection and Immunity  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0066-8026","authenticated-orcid":false,"given":"Chen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Melbourne, Located at the Peter Doherty Institute for Infection and Immunity  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2657-0048","authenticated-orcid":false,"given":"Brooke J.","family":"Wanrooy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Melbourne, Located at the Peter Doherty Institute for Infection and Immunity  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9217-6497","authenticated-orcid":false,"given":"Ashlyn S.","family":"Kerr","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Melbourne, Located at the Peter Doherty Institute for Infection and Immunity  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Melbourne, Located at the Peter Doherty Institute for Infection and Immunity  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron G.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Melbourne, Located at the Peter Doherty Institute for Infection and Immunity  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0576-5462","authenticated-orcid":false,"given":"Heran","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Melbourne, Located at the Peter Doherty Institute for Infection and Immunity  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1752-9579","authenticated-orcid":false,"given":"Linda M.","family":"Wakim","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Melbourne, Located at the Peter Doherty Institute for Infection and Immunity  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2260-0026","authenticated-orcid":false,"given":"Ashraful","family":"Haque","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Melbourne, Located at the Peter Doherty Institute for Infection and Immunity  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,11]]},"reference":[{"issue":"3","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/s41587-020-0739-1","article-title":"Highly Sensitive Spatial Transcriptomics at Near\u2010Cellular Resolution With Slide\u2010seqV2","volume":"39","author":"Stickels R. 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