HIV-infected T cells are migratory vehicles for viral dissemination

Using intravital microscopy, this study visualizes HIV-1-infected T cells within the lymph nodes of humanized mice, demonstrating that infected cells have reduced motility and long membrane processes; treating infected mice with a lymphocyte egress inhibitor prevents HIV-1 from spreading to the circulation during the course of treatment. HIV-infected cells pictured in vivo This study provides a first glimpse of the behaviour of HIV-infected cells in a living animal, revealing completely unanticipated events. Using multiphoton intravital microscopy, Thomas Murooka et al . visualize HIV-1 infected T cells in the lymph nodes of humanized mice. The authors observe reduced cell motility, and the presence of long membrane processes on infected cells. Treating infected mice with a lymphocyte-egress inhibitor prevented the spread of HIV-1 into the circulation, although this inhibition persisted only during treatment. After host entry through mucosal surfaces, human immunodeficiency virus-1 (HIV-1) disseminates to lymphoid tissues to establish a generalized infection of the immune system. The mechanisms by which this virus spreads among permissive target cells locally during the early stages of transmission and systemically during subsequent dissemination are not known 1 . In vitro studies suggest that the formation of virological synapses during stable contacts between infected and uninfected T cells greatly increases the efficiency of viral transfer 2 . It is unclear, however, whether T-cell contacts are sufficiently stable in vivo to allow for functional synapse formation under the conditions of perpetual cell motility in epithelial 3 and lymphoid tissues 4 . Here, using multiphoton intravital microscopy, we examine the dynamic behaviour of HIV-infected T cells in the lymph nodes of humanized mice. We find that most productively infected T cells migrate robustly, resulting in their even distribution throughout the lymph node cortex. A subset of infected cells formed multinucleated syncytia through HIV envelope-dependent cell fusion. Both uncoordinated motility of syncytia and adhesion to CD4 + lymph node cells led to the formation of long membrane tethers, increasing cell lengths to up to ten times that of migrating uninfected T cells. Blocking the egress of migratory T cells from the lymph nodes into efferent lymph vessels, and thus interrupting T-cell recirculation, limited HIV dissemination and strongly reduced plasma viraemia. Thus, we have found that HIV-in