title: Access of HIV-2 to CD169-dependent dendritic cell-mediated trans infection pathway is attenuated.
abstract: The mechanisms behind the low viral loads and lower mortality rates of HIV-2(+) individuals remain unknown. We hypothesized that reduced interaction of HIV-2 with CD169, the primary HIV-1 attachment factor on monocyte-derived dendritic cells (DCs) that targets captured virus particles to the trans infection pathway, contributes to its diminished pathogenic phenotype in vivo. We observed a significant decrease in capture of HIV-2 Gag-eGFP virus-like particles (VLPs) and infectious GFP-containing HIV-2 particles compared to corresponding HIV-1 particles by CD169(+) mature DCs. Interestingly, there was decreased co-localization of HIV-2 with HIV-1 Gag at plasma membrane microdomains in virus producer cells which correlated with reduced incorporation of GM3, the CD169 ligand, in HIV-2 virions, and reduction in mature DC-mediated HIV-2 trans infection compared to HIV-1. We conclude that limited interaction of HIV-2 with CD169 diminishes virus access to the mature DC-mediated trans infection pathway and might result in attenuated HIV-2 dissemination in vivo.
authors: Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: sgeer@bu.edu.
authors: Suzanne D G
authors: SDG
authors: Kijewski
authors: Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: hakiyama@bu.edu.
authors: Hisashi
authors: H
authors: Akiyama
authors: Department of Chemistry and The Photonics Center, Boston University, Boston, MA 02215, USA. Electronic address: feizpour@bu.edu.
authors: Amin
authors: A
authors: Feizpour
authors: Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: cm12@bu.edu.
authors: Caitlin M
authors: CM
authors: Miller
authors: Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: Nora-guadalupe.Ramirez@utsouthwestern.edu.
authors: Nora-Guadalupe P
authors: NP
authors: Ramirez
authors: Department of Chemistry and The Photonics Center, Boston University, Boston, MA 02215, USA. Electronic address: bmr@bu.edu.
authors: Björn M
authors: BM
authors: Reinhard
authors: Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: rgummulu@bu.edu.
authors: Suryaram
authors: S
authors: Gummuluru
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D015498:HIV-2 / Q000502:physiology*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014771:Virion; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D011993:Recombinant Fusion Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D000099192:CD69 Antigens
keywords: CD169; Cell-associated virus transfer; Dendritic cells; GM3; HIV-2; Trans infection; Virus capture