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Open Access

Different routes of entry of HTLV-1 during infection of primary dendritic cells and CD4+ T cells

  • Kathryn S Jones1Email author,
  • Cari Petrow-Sadowski1,
  • Daniel C Bertolette2,
  • Nabela Enam3,
  • Rachel K Bagni3,
  • Stig MR Jensen2, 4,
  • David A Davis5,
  • Robert Yarchoan5 and
  • Francis W Ruscetti2
Retrovirology201411(Suppl 1):O77

Published: 7 January 2014


PeptideInfectious DiseaseCancer ResearchDendritic CellHost Cell

Although HTLV-1 is primarily found in T cells in infected individuals, ex vivo cultures of T cells are not readily infected by cell-free HTLV-1. In contrast, cell-free HTLV-1 efficiently infects cultures of primary dendritic cells. Little is known about the productive route of infection of dendritic cells, or the stage at which infection of T cells is blocked. Comparison of primary CD4+ T cells and monocyte-derived dendritic cells (MDDC) exposed to HTLV-1 revealed that, for both cell types, HTLV-1 virions bound to and entered the cells. Entry was dependent on interactions with HSPGs and neuropilin-1, molecules known to be involved in HTLV-1 entry. The observation that cell-free HTLV-1 can enter both types of cells but only efficiently infect DCs suggests that the virus can enter cells by both productive and non-productive pathways. Dendritic cells use a type of constitutive, actin-dependent endocytosis called macropinocytosis to capture antigens, and several viruses use this route to infect host cells. In T cells, macropinocytosis is not constitutive, but can be induced. Studies with inhibitors revealed that HTLV-1 infection of MDDC is markedly decreased when the cells are treated with an actin-depolymerizing agent (cytochalasin D) or a specific inhibitor of macropinocytosis (EIPA). Strikingly, treatment of primary CD4+ T cells with a peptide that induces macropinocytosis dramatically increases infection following exposure to cell-free HTLV-1. These results suggest that HTLV-1 can enter cells by both productive and non-productive pathways, and that altering the route of entry can alter the susceptibility of a given cell type to HTLV-1 infection.

Authors’ Affiliations

Frederick National Laboratory for Cancer Research, Basic Research Program, Cancer and Inflammation Program, SAIC-Frederick, Inc, Frederick, USA
Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, USA
Protein Expression Laboratory, Frederick National Laboratory for Cancer Research, Advanced Technology Program, SAIC-Frederick, Inc, Frederick, USA
National Institute of Allergy and Infectious Diseases, Bethesda, USA
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, USA


© Jones et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.