title: Trans-infection but not infection from within endosomal compartments after cell-to-cell HIV-1 transfer to CD4+ T cells.
abstract: Cellular contacts between HIV-1-infected donor cells and uninfected primary CD4(+) T lymphocytes lead to virus transfer into endosomes. Recent evidence suggests that HIV particles may fuse with endosomal membranes to initiate a productive infection. To explore the role of endocytosis in the entry and replication of HIV, we evaluated the infectivity of transferred HIV particles in a cell-to-cell culture model of virus transmission. Endocytosed virus led to productive infection of cells, except when cells were cultured in the presence of the anti-gp120 mAb IgGb12, an agent that blocks virus attachment to CD4, suggesting that endocytosed virus was recycled to the outer cell surface. Confocal microscopy confirmed the colocalization of internalized virus antigen and the endosomal marker dynamin. Additionally, virus transfer, fusion, or productive infection was not blocked by dynasore, dynamin-dependent endosome-scission inhibitor, at subtoxic concentrations, suggesting that the early capture of virus into intracellular compartments did not depend on endosomal maturation. Our results suggest that endocytosis is not a mechanism of infection of primary CD4 T cells, but may serve as a reservoir capable of inducing trans-infection of cells after the release of HIV particles to the extracellular environment.
authors: IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain.
authors: Marc
authors: M
authors: Permanyer
authors: Ester
authors: E
authors: Ballana
authors: Roger
authors: R
authors: Badia
authors: Eduardo
authors: E
authors: Pauls
authors: Bonaventura
authors: B
authors: Clotet
authors: José A
authors: JA
authors: Esté
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001596:Benzylamines; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology*; D018920:Coculture Techniques; D000080027:Cyclams; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism* / Q000821:virology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000378:metabolism*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007963:Leukocytes, Mononuclear / Q000166:cytology; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D001596:Benzylamines; D000080027:Cyclams; D015699:HIV Envelope Protein gp120; D006571:Heterocyclic Compounds; D007074:Immunoglobulin G; C514793:gp120 protein, Human immunodeficiency virus 1; C088327:plerixafor