title: Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication.
abstract: Human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1) are complex retroviruses mainly infecting CD4(+) T lymphocytes. In addition, antigen-presenting cells such as dendritic cells (DCs) are targeted in vivo by both viruses, although to a lesser extent. Interaction of HIV-1 with DCs plays a key role in viral dissemination from the mucosa to CD4(+) T lymphocytes present in lymphoid organs. While similar mechanisms may occur for HTLV-1 as well, most HTLV-1 data were obtained from T-cell studies, and little is known regarding the trafficking of this virus in DCs. We first compared the efficiency of cell-free versus cell-associated viral sources of both retroviruses at infecting DCs. We showed that both HIV-1 and HTLV-1 cell-free particles are poorly efficient at productively infecting DCs, except when DC-SIGN has been engaged. Furthermore, while SAMHD-1 accounts for restriction of cell-free HIV-1 infection, it is not involved in HTLV-1 restriction. In addition, cell-free viruses lead mainly to a nonproductive DC infection, leading to trans-infection of T-cells, a process important for HIV-1 spread but not for that of HTLV-1. Finally, we show that T-DC cell-to-cell transfer implies viral trafficking in vesicles that may both increase productive infection of DCs ("cis-infection") and allow viral escape from immune surveillance. Altogether, these observations allowed us to draw a model of HTLV-1 and HIV-1 trafficking in DCs.
authors.affiliation: Equipe Oncogenèse Rétrovirale, Equipe Labellisée Ligue Nationale Contre le Cancer, Centre International de Recherche en Infectiologie INSERM U1111-CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université de Lyon 1, and LabEx ECOFECT, Université Lyon, Lyon, France helene.dutartre@ens-lyon.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: Dutartre
authors.affiliation: Equipe Oncogenèse Rétrovirale, Equipe Labellisée Ligue Nationale Contre le Cancer, Centre International de Recherche en Infectiologie INSERM U1111-CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université de Lyon 1, and LabEx ECOFECT, Université Lyon, Lyon, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Clavière
authors.affiliation: Equipe Oncogenèse Rétrovirale, Equipe Labellisée Ligue Nationale Contre le Cancer, Centre International de Recherche en Infectiologie INSERM U1111-CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université de Lyon 1, and LabEx ECOFECT, Université Lyon, Lyon, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Journo
authors.affiliation: Equipe Oncogenèse Rétrovirale, Equipe Labellisée Ligue Nationale Contre le Cancer, Centre International de Recherche en Infectiologie INSERM U1111-CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université de Lyon 1, and LabEx ECOFECT, Université Lyon, Lyon, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Mahieux
mesh_terms: D001692:Biological Transport; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D003713:Dendritic Cells / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D053586:Virus Internalization; D057074:Virus Release; D014779:Virus Replication