4.6 Article

In vitro derived dendritic cells trans-infect CD4 T cells primarily with surface-bound HIV-1 virions

Journal

PLOS PATHOGENS
Volume 3, Issue 1, Pages 38-45

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.0030004

Keywords

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Funding

  1. NCRR NIH HHS [1S10 RR022448, S10 RR022448, C06 RR018928, RR 18928-01] Funding Source: Medline
  2. NIAID NIH HHS [P30 AI27763, R03 AI062263, P30 AI027763] Funding Source: Medline
  3. NICHD NIH HHS [P01 HD040543, P01 HD40543] Funding Source: Medline
  4. NIMHD NIH HHS [L60 MD003100] Funding Source: Medline

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In the prevailing model of HIV-1 trans-infection, dendritic cells (DCs) capture and internalize intact virions and transfer these virions to interacting T cells at the virological synapse. Here, we show that HIV-1 virions transmitted in trans from in vitro derived DCs to T cells principally originate from the surface of DCs. Selective neutralization of surface-bound virions abrogated trans-infection by monocyte-derived DCs and CD34-derived Langerhans cells. Under conditions mimicking antigen recognition by the interacting T cells, most transferred virions still derived from the cell surface, although a few were transferred from an internal compartment. Our findings suggest that attachment inhibitors could neutralize trans-infection of T cells by DCs in vivo.

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