title: The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry.
abstract: Dengue viruses (DVs) are responsible for the most medically relevant arboviral diseases. However, the molecular interactions mediating DV entry are poorly understood. We determined that TIM and TAM proteins, two receptor families that mediate the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, serve as DV entry factors. Cells poorly susceptible to DV are robustly infected after ectopic expression of TIM or TAM receptors. Conversely, DV infection of susceptible cells is inhibited by anti-TIM or anti-TAM antibodies or knockdown of TIM and TAM expression. TIM receptors facilitate DV entry by directly interacting with virion-associated PtdSer. TAM-mediated infection relies on indirect DV recognition, in which the TAM ligand Gas6 acts as a bridging molecule by binding to PtdSer within the virion. This dual mode of virus recognition by TIM and TAM receptors reveals how DVs usurp the apoptotic cell clearance pathway for infectious entry.
authors.affiliation: INSERM U944, Laboratoire de Pathologie et Virologie Moléculaire, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Meertens
authors.forename: Xavier
authors.initials: X
authors.lastname: Carnec
authors.forename: Manuel Perera
authors.initials: MP
authors.lastname: Lecoin
authors.forename: Rasika
authors.initials: R
authors.lastname: Ramdasi
authors.forename: Florence
authors.initials: F
authors.lastname: Guivel-Benhassine
authors.forename: Erin
authors.initials: E
authors.lastname: Lew
authors.forename: Greg
authors.initials: G
authors.lastname: Lemke
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
authors.forename: Ali
authors.initials: A
authors.lastname: Amara
mesh_terms: D000818:Animals; D002460:Cell Line; D003716:Dengue Virus / Q000502:physiology*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology*; D053586:Virus Internalization
chemical_list: D011956:Receptors, Cell Surface; D011991:Receptors, Virus; C408123:phosphatidylserine receptor