Longitudinal imaging of HIV-1 spread in humanized mice with parallel 3D immunofluorescence and electron tomography

摘要: Dissemination of HIV-1 throughout lymphoid tissues leads to systemic virus spread following infection. We combined tissue clearing, 3D-immunofluorescence, and electron tomography (ET) longitudinally assess early in humanized mice. Immunofluorescence revealed peak infection density gut at 10-12 days post-infection when blood viral loads were low. Human CD4+ T-cells HIV-1-infected cells localized predominantly crypts the lower third intestinal villi. Free virions infected not readily detectable by ET 5-days post-infection, whereas surrounded pools free present ~10% days. spleen thousands released individual discreet cytoplasmic densities near sites prolific production. These studies highlight importance multiscale imaging are adaptable other animal models human patient samples.