title: HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits.
abstract: Contact-dependent communication between immune cells generates protection but also facilitates viral spread. Here we found that macrophages formed long-range actin-propelled conduits in response to negative factor (Nef), a human immunodeficiency virus type 1 (HIV-1) protein with immunosuppressive functions. Conduits attenuated immunoglobulin G2 (IgG2) and IgA class switching in systemic and intestinal lymphoid follicles by shuttling Nef from infected macrophages to B cells through a guanine-exchange factor-dependent pathway involving the amino-terminal anchor, central core and carboxy-terminal flexible loop of Nef. By showing stronger virus-specific IgG2 and IgA responses in patients with Nef-deficient virions, our data suggest that HIV-1 exploits intercellular 'highways' as a 'Trojan horse' to deliver Nef to B cells and evade humoral immunity systemically and at mucosal sites of entry.
authors: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York, USA.
authors: Weifeng
authors: W
authors: Xu
authors: Paul A
authors: PA
authors: Santini
authors: John S
authors: JS
authors: Sullivan
authors: Bing
authors: B
authors: He
authors: Meimei
authors: M
authors: Shan
authors: Susan C
authors: SC
authors: Ball
authors: Wayne B
authors: WB
authors: Dyer
authors: Thomas J
authors: TJ
authors: Ketas
authors: Amy
authors: A
authors: Chadburn
authors: Leona
authors: L
authors: Cohen-Gould
authors: Daniel M
authors: DM
authors: Knowles
authors: April
authors: A
authors: Chiu
authors: Rogier W
authors: RW
authors: Sanders
authors: Kang
authors: K
authors: Chen
authors: Andrea
authors: A
authors: Cerutti
mesh_terms: D000199:Actins / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000502:physiology; D002450:Cell Communication; D018858:Germinal Center / Q000502:physiology; D015483:HIV Antibodies / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000502:physiology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000276:immunology*; D008264:Macrophages / Q000821:virology; D020298:U937 Cells; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000502:physiology*
chemical_list: D000199:Actins; D019013:CD40 Antigens; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C514799:p24 protein, Human Immunodeficiency Virus Type 1