Dual host-pathogen screening of the lung during severe influenza using spatial transcriptomics

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 ten 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-type harboured viral transcripts, suggesting indiscriminate infection across the specific area of tissue examined.

Subsequent whole-section immunohistochemical assessment further supported the phenomenon of localised 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.