The Spatial Biology of HIV Transmission and Infection: Imaging the Female and Male Reproductive Tracts

HIV transmission through the female and male reproductive tracts is governed by spatially organized interactions between virions, epithelial barriers, and tissue-resident immune cells. 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-based IHC and ISH established foundational maps of infected cells within intact mucosa, revealing regional immune heterogeneity and linking susceptibility to barrier integrity and target-cell density. Fluorescent virion imaging extended these findings by visualizing viral movement across mucosal surfaces and the first contacts with permissive cells. In parallel, non-human 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-sheet 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.