PMID- 18804253 OWN - NLM STAT- MEDLINE DCOM- 20081223 LR - 20181113 IS - 1096-0341 (Electronic) IS - 0042-6822 (Print) IS - 0042-6822 (Linking) VI - 381 IP - 1 DP - 2008 Nov 10 TI - Macropinocytosis and cytoskeleton contribute to dendritic cell-mediated HIV-1 transmission to CD4+ T cells. PG - 143-54 LID - 10.1016/j.virol.2008.08.028 [doi] AB - Dendritic cells (DCs) are among the first immune cells to encounter HIV-1 at the initial infection. DCs efficiently transfer HIV-1 to CD4+ T cells via infectious or virological synapses formed between DCs and T cells. Retroviruses exploit the cytoskeletal network to facilitate viral infection and dissemination; however, the role of the cytoskeleton in DC-mediated HIV-1 transmission is unknown. Here, we report that intact cytoskeleton is essential for DC-mediated HIV-1 transmission to CD4+ T cells. We found that macropinocytosis of HIV-1 contributes to DC-mediated HIV-1 endocytosis and transmission. Blocking HIV-1 macropinocytosis and disrupting actin or microtubules in DCs with specific inhibitors significantly prevented DC-mediated HIV-1 trans-infection of CD4+ T cells. Altered HIV-1 trafficking and impaired formation of virological synapses primarily accounted for the inhibition of viral transmission by cytoskeletal inhibitors. Our results provide new insights into the mechanisms underlying DC-mediated HIV-1 transmission to CD4+ T cells via the cytoskeletal network. FAU - Wang, Jian-Hua AU - Wang JH AD - Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. FAU - Wells, Clive AU - Wells C FAU - Wu, Li AU - Wu L LA - eng GR - 1S10RR022412-01/RR/NCRR NIH HHS/United States GR - AI068493/AI/NIAID NIH HHS/United States GR - S10 RR022412/RR/NCRR NIH HHS/United States GR - R01 AI068493-03/AI/NIAID NIH HHS/United States GR - R01 AI068493/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080918 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (Actins) RN - 0 (Free Radical Scavengers) RN - 0 (Tubulin Modulators) RN - SH1WY3R615 (Nocodazole) RN - YOW8V9698H (Dimethyl Sulfoxide) SB - IM MH - Actins/metabolism MH - CD4-Positive T-Lymphocytes/metabolism/*virology MH - Cells, Cultured MH - Cytoskeleton/*metabolism MH - Dendritic Cells/drug effects/metabolism/ultrastructure/*virology MH - Dimethyl Sulfoxide/pharmacology MH - Free Radical Scavengers/pharmacology MH - HIV Infections/*transmission/virology MH - HIV-1/*physiology MH - Humans MH - Nocodazole/pharmacology MH - Pinocytosis/*physiology MH - Tubulin Modulators/pharmacology PMC - PMC2575140 MID - NIHMS65955 EDAT- 2008/09/23 09:00 MHDA- 2008/12/24 09:00 PMCR- 2009/11/10 CRDT- 2008/09/23 09:00 PHST- 2008/07/11 00:00 [received] PHST- 2008/08/12 00:00 [revised] PHST- 2008/08/15 00:00 [accepted] PHST- 2008/09/23 09:00 [pubmed] PHST- 2008/12/24 09:00 [medline] PHST- 2008/09/23 09:00 [entrez] PHST- 2009/11/10 00:00 [pmc-release] AID - S0042-6822(08)00550-3 [pii] AID - 10.1016/j.virol.2008.08.028 [doi] PST - ppublish SO - Virology. 2008 Nov 10;381(1):143-54. doi: 10.1016/j.virol.2008.08.028. Epub 2008 Sep 18.