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Imaging approaches have been central to defining these earliest events, progressing from classical histology and immunohistochemistry (IHC) to modern fluorescence, multiphoton microscopy, tissue clearing, and spatially resolved molecular platforms. Early FFPE\u2010based IHC and ISH established foundational maps of infected cells within intact mucosa, revealing regional immune heterogeneity and linking susceptibility to barrier integrity and target\u2010cell density. Fluorescent virion imaging extended these findings by visualizing viral movement across mucosal surfaces and the first contacts with permissive cells. In parallel, non\u2010human primate (NHP) models enabled temporal resolution of initial SIV infection foci and dissemination patterns under controlled exposure conditions. More recent techniques, including RNAscope and DNAscope, light\u2010sheet microscopy, multiplex fluorescence, and PET\/CT, allow quantitative mapping of viral nucleic acids, reservoir populations, and immune microenvironments across whole tissues and organs. Together, these spatial imaging platforms have demonstrated that HIV establishes infection within discrete mucosal niches that vary by anatomical site and immune architecture. Integrated imaging increasingly reveals how HIV behaves within the distinct mucosal environments of the female and male reproductive tracts.<\/jats:p>","DOI":"10.1111\/aji.70261","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T12:11:27Z","timestamp":1780056687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Spatial Biology of HIV Transmission and Infection: Imaging the Female and Male Reproductive Tracts"],"prefix":"10.1111","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1305-254X","authenticated-orcid":false,"given":"Ann M.","family":"Carias","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia 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