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Macropinocytosis and cytoskeleton contribute to dendritic cell-mediated HIV-1 transmission to CD4+ T cells

Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Virology (Impact Factor: 3.28). 10/2008; 381(1):143-54. DOI: 10.1016/j.virol.2008.08.028
Source: PubMed

ABSTRACT 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.

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