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Recent studies reveal that actin-rich membrane extensions establish direct contact between cells at this synapse and facilitate virus transmission. Genesis of these contacts involves signaling through c-Src and Cdc42, which modulate actin polymerization and filopodia formation via the Arp2\/3 complex and Diaphanous 2 (Diaph2). We found that Slit2N, a ligand for the Roundabout (Robo) receptors, blocked HIV-1-induced signaling through Arp2\/3 and Diaph2, decreased filopodial extensions on dendritic cells and inhibited cell-to-cell transmission of HIV-1 in a Robo1-dependent manner. Employing proteomic analysis, we identified Flightless-1 as a novel, Robo1-interacting protein. Treatment with shRNAs reduced levels of Flightless-1 and demonstrated its role in efficient cell-to-cell transfer of HIV-1. These results suggest a novel strategy to limit viral infection in the host by targeting the Slit\/Robo pathway with modulation of cytoskeletal elements previously unrecognized in HIV-1 transmission.<\/jats:p>","DOI":"10.1038\/srep16833","type":"journal-article","created":{"date-parts":[[2015,11,19]],"date-time":"2015-11-19T10:10:42Z","timestamp":1447927842000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Slit2N Inhibits Transmission of HIV-1 from Dendritic Cells to T-cells by Modulating Novel Cytoskeletal Elements"],"prefix":"10.1038","volume":"5","author":[{"given":"Ashutosh","family":"Shrivastava","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Prasad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula M.","family":"Kuzontkoski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome E.","family":"Groopman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,11,19]]},"reference":[{"key":"BFsrep16833_CR1","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1002\/rmv.1753","volume":"23","author":"AN Harman","year":"2013","unstructured":"Harman, A. 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