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Macropinocytosis and cytoskeleton contribute to dendritic cell-mediated HIV-1 transmission to CD4 + T cells
Journal article   Open access   Peer reviewed

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

Jian-Hua Wang, Clive Wells and Li Wu
Virology (New York, N.Y.), Vol.381(1), pp.143-154
2008
DOI: 10.1016/j.virol.2008.08.028
PMCID: PMC2575140
PMID: 18804253
url
https://doi.org/10.1016/j.virol.2008.08.028View
Published (Version of record) Open Access

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.
Cytoskeleton HIV-1 CD4 + T cells Dendritic cells Transmission Macropinocytosis

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