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dc.contributor.authorMurooka, Thomas
dc.contributor.authorDeruaz, Maud
dc.contributor.authorMarangoni, Francesco
dc.contributor.authorVrbanac, Vladimir
dc.contributor.authorSeung, Edward N.
dc.contributor.authorVon Andrian, Ulrich H.
dc.contributor.authorTager, Andrew Martin
dc.contributor.authorLuster, Andrew David
dc.contributor.authorMempel, Thorsten Roman
dc.date.accessioned2013-10-17T18:11:45Z
dc.date.issued2012
dc.identifier.citationMurooka, Thomas T., Maud Deruaz, Francesco Marangoni, Vladimir D. Vrbanac, Edward Seung, Ulrich H. von Andrian, Andrew M. Tager, Andrew D. Luster, and Thorsten R. Mempel. 2012. HIV-infected T cells are migratory vehicles for viral dissemination. Nature 490(7419): 283-287.en_US
dc.identifier.issn0028-0836en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11181001
dc.description.abstractAfter host entry through mucosal surfaces, 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 early stages of transmission, and systemically during subsequent dissemination are not known1. In vitro studies suggest that formation of virological synapses (VSs) during stable contacts between infected and uninfected T cells greatly increases the efficiency of viral transfer2. It is unclear, however, if T cell contacts are sufficiently stable in vivo to allow for functional synapse formation under the conditions of perpetual cell motility in epithelial3 and lymphoid tissues4. Here, using multiphoton intravital microscopy (MP-IVM), we examined the dynamic behavior of HIV-infected T cells in lymph nodes (LNs) of humanized mice. We found that most productively infected T cells migrated robustly, resulting in their even distribution throughout the LN cortex. A subset of infected cells formed multinucleated syncytia through HIV envelope (Env)-dependent cell fusion. Both uncoordinated motility of syncytia as well as adhesion to CD4+ LN cells led to the formation of long membrane tethers, increasing cell lengths to up to 10 times that of migrating uninfected T cells. Blocking the egress of migratory T cells from LNs into efferent lymph, and thus interrupting T cell recirculation, limited HIV dissemination and strongly reduced plasma viremia. Thus, we have found that HIV-infected T cells are motile, form syncytia, and establish tethering interactions that may facilitate cell-to-cell transmission through VSs. While their migration in LNs spreads infection locally, T cell recirculation through tissues is important for efficient systemic viral spread, suggesting new molecular targets to antagonize HIV infection.en_US
dc.language.isoen_USen_US
dc.relation.isversionofdoi:10.1038/nature11398en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3470742/pdf/en_US
dash.licenseLAA
dc.subjectHuman Immunodeficiency Virus (HIV)-1en_US
dc.subjectCell Migrationen_US
dc.subjectLymph Node (LN)en_US
dc.subjectMultiphoton Intravital Microscopy (MP-IVM)en_US
dc.subjectHumanized Miceen_US
dc.subjectT cell Traffickingen_US
dc.titleHIV-infected T cells are migratory vehicles for viral disseminationen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalNatureen_US
dash.depositing.authorMempel, Thorsten Roman
dc.date.available2013-10-17T18:11:45Z
dc.identifier.doi10.1038/nature11398*
dash.authorsorderedfalse
dash.contributor.affiliatedMarangoni, Francesco
dash.contributor.affiliatedMempel, Thorsten
dash.contributor.affiliatedvon Andrian-Werburg, Ulrich
dash.contributor.affiliatedMurooka, Thomas
dash.contributor.affiliatedSeung, Edward N.
dash.contributor.affiliatedLuster, Andrew
dash.contributor.affiliatedTager, Andrew Martin
dash.contributor.affiliatedDeruaz, Maud


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